Cancers, Volume 18, Issue 10 (May-2 2026) – 180 articles

Background: Spleen-preserving (SP) distal pancreatectomy (DP) with splenic vessels resection (SVR) (Warsaw procedure, WP) is an option for the treatment of tumors with low malignant potential. The reverse blood flow through the short gastric arteries (SGA) explains the preservation of the spleen after SVR, but leaves the source of the blood supply to the SGAs hidden. The types of blood supply to the spleen after WP and their incidence have not been previously described, nor has the significance of these types for locally advanced pancreatic head cancer (LAPHC) surgery been determined. Aim: To determine the main types of spleen blood supply after WP, and to assess the feasibility and safety of splenic artery (SA) rotation for the organ-preserving surgery of LAPHC. Methods: Retrospective analyses of demographic and perioperative data, including CT scans, overall (OS) and progression-free (PFS) survival after 71 SP DP SVR and 41 SP SVR pancreaticoduodenectomies (PD) and total pancreatectomies (TP) for LAPHC (2007–2025). Results: In 134 SP procedures, SA was resected in 115 cases (71DP, 9 TP, 3 central, and 32 PD). Indications for surgery were MCN (41), IPMN (14), CSA (3), NEN (25), SPPN (8), PHDAC (40), sarcoma (1), autoimmune (1), and calculous chronic pancreatitis (1). There were no deaths or ischemia-related splenectomies. Morbidity—31% (n23); Dindo–Clavien (D-C) > 3b-2.8%; POPF-grade B-n7 (10.6%); splenic infarctions on CT after SVR-n18 (23%), one symptomatic. CT revealed three types of arterial blood supply to the spleen after SPDP SVR: left gastric artery (LGA) type (n50, 70, 5%), gastro-epyploic arcade (GEA) type (n9, 12, 5%), and an intermediate type (n12, 17%). Spleen- and pancreas tail-preserving SVR pancreatectomies for LAPHC (n41) were accompanied by rotation of the SA to substitute resected SMA (n19) and CHA (n15) for 26 Whipples and 8TPs. There were no ischemic complications. D-C > 3–19.5%. Median OS and PFS for PDAC were 35 and 21 months for 29.5 months median follow-up. Conclusions: Despite the preservation of blood flow through all potential sources of splenic blood supply following resection of the splenic artery, the main collaterals supplying the spleen after WP are LGA branches (~90%). This knowledge, with strict adherence to the developed criteria, allows for the safe preservation of the spleen, pancreatic tail, and stomach during pancreatectomies with SA resection, including its rotation for the substitution of the SMA and CHA in LAPHC. Full article

Background: The rising incidence of CINIII, particularly in younger patients, has highlighted limitations of current surgical treatments, which can affect fertility and carry recurrence risks. This underscores an urgent clinical need for non-invasive therapies. Our study addresses this by investigating the cellular and molecular changes during CINIII progression to cervical squamous cell carcinoma (CSCC). Methods: We employed single-cell sequencing to meticulously analyze cell types and molecular mechanisms within cervical epithelial cells and their microenvironment throughout the CINIII-to-CSCC transition. Results: Key findings include the identification of Sox2 and its signaling pathway as markers for specific cervical stem cells (CCSCs) during malignant transformation. In the microenvironment, upregulated VWF, MMP2, and HTRA1 were observed in vascular endothelial cells, while TXNIP+ and ARL4D+ fibroblasts underwent transformation into myofibroblasts. Immune cell proportions notably increased, particularly macrophages, T cells, B cells, NK cells, mast cells, and neutrophils, contrasting with a decrease in non-immune cells. Furthermore, interaction analysis revealed that communication between macrophages and cervical epithelial cells was the most prominent. Conclusions: This research comprehensively details the complex cellular and molecular remodeling inherent in CINIII progression. By pinpointing specific pathways and cell populations, our findings establish a crucial framework for developing innovative, non-invasive drug therapies to delay disease progression and ultimately improve long-term reproductive outcomes for patients. Full article

Background/Objectives: Body-surface-area-based dosing of continuous-infusion 5-fluorouracil does not account for inter-individual pharmacokinetic variability. This pilot study explored whether patient-level representative plasma 5-fluorouracil exposure within the target area under the concentration–time curve (AUC) range was associated with clinical outcomes. It evaluated a prototype immunochromatographic assay as a preliminary monitoring tool. Methods: Fifteen patients with unresectable advanced or recurrent colorectal cancer who received continuous-infusion 5-fluorouracil-based chemotherapy were prospectively evaluated between 1 January 2017 and 30 April 2018. Plasma 5-fluorouracil levels were measured during eight treatment cycles at three time points in each cycle. Representative AUC values were calculated using median concentrations across cycles and interpreted as exploratory patient-level exposure indices. Tumor response, grade ≥2 adverse events, progression-free survival, and overall survival were assessed descriptively. Results: The median representative AUC was 24.3 mg·h/L. Eight patients (53.3%) were within the target range of 20–30 mg·h/L, whereas seven (46.7%) were outside it. Disease control was observed in 7 of 8 patients (87.5%) within the target range and in 3 of 7 patients (42.9%) outside it. Grade ≥2 adverse events were less frequent in the target-range group (2/8, 25.0%) than in the outside-range group (6/7, 85.7%; p = 0.041). Progression-free survival was numerically longer in the target-range group (17.2 vs. 9.2 months, p = 0.36), while overall survival did not differ clearly (p = 0.76); these survival analyses were exploratory. The prototype immunochromatographic assay showed a favorable correlation with the My-5FU assay (R2 = 0.762), but Bland–Altman analysis showed relatively wide limits of agreement. Conclusions: Target plasma 5-fluorouracil exposure was associated with lower clinically relevant toxicity and may support favorable tumor control in this pilot cohort. The prototype immunochromatographic method demonstrated preliminary feasibility for rapid plasma 5-FU monitoring but requires further validation before routine dose adjustment. Full article

Cutaneous melanoma is an aggressive skin cancer. While laser therapy is established for non-melanoma skin cancers, its role in melanoma remains controversial and largely unsupported by robust clinical evidence. The gold standard for melanoma management remains surgical excision, as it allows for definitive histopathological diagnosis, Breslow thickness measurement, and surgical margin assessment, which are essential for accurate staging. This narrative review analyzed preclinical and clinical studies evaluating various laser modalities, including Nd:YAG, CO₂, pulsed dye, photodynamic therapy (PDT) and photothermal therapy (PTT), for efficacy, recurrence rates, and limitations in cutaneous melanoma management. Nd:YAG laser (1064 nm) showed potential for local control in thin stage I melanomas, reporting a low local recurrence rate of 0–0.7% and favorable 5-year survival in small, non-randomized cohorts. CO₂ laser (10,600 nm) provides effective palliation and local control for in-transit or unresectable metastases, but local recurrence is highly variable, reaching up to 46.7%. Photodynamic therapy showed variable efficacy, although Chlorin e6 achieved complete local regression in a small series of metastases. A critical limitation of laser therapy is the irreversible destruction of tissue, which precludes these vital assessments. Therefore, laser treatment should be cautiously reserved for cases where standard surgery is not feasible, acknowledging that it may interfere with the evaluation of curative outcomes and accurate staging. Laser therapy is a valuable minimally invasive adjunct for local control in selected patients who are poor surgical candidates or require palliative care. Routine use is restricted by the lack of randomized controlled trials. Future studies should prioritize combination strategies with systemic or immunotherapeutic approaches to enhance overall outcomes. Full article

Background: Lymphocyte-activation gene 3 (LAG3) and cytotoxic T-lymphocyte-associated protein 4 (CTLA4) are immune checkpoint receptors and inhibitory regulators of T-cells. Methods: Here, we analyzed the prevalence and potential impact of the LAG3 gene variant rs870849 and the CTLA4 gene variant rs231775 in AML patients eligible for autologous stem cell transplantation. Results: While CTLA4 rs231775 was prevalent at reduced minor allele frequencies (MAF 0.33), LAG3 rs870849 was prevalent at elevated minor allele frequencies (MAF 0.58) in AML patients, compared to the allele frequencies in the European population (MAF 0.37 and MAF 0.39). The gene risk analysis indicated a dose-dependent risk of AML disease associated with LAG3 rs870849, but no risk associated with CTLA4 rs231775. Baseline blood count profiles differed across LAG3 genotypes, suggesting a link between LAG3 rs870849 and disease-associated levels of anemia, thrombocytopenia and peripheral blast percentage. Conslusions: The germline LAG3 variant rs870849 may be associated with AML disease risk and specific hematological disease features. Full article

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer type in which therapeutic options are limited, and the disease is characterized by a poor prognosis. In the development of pancreatic cancer, dysregulated Ca²⁺ signaling plays a key role by regulating proliferation, survival, metabolic adaptation, and tumor–microenvironment interactions. Among the Ca²⁺ channels, TRPV6 has emerged as a key regulator since this channel is highly selective for Ca²⁺ and frequently overexpressed in different types of cancers. The aim of this review is to summarize our current knowledge on the structure, regulation, and function of TRPV6, with emphasis on its cell-type specific roles within the pancreas. We describe the mechanisms by which TRPV6-mediated Ca²⁺ influx activates oncogenic signaling pathways, such as NFAT, AKT/mTOR, and NF-κB, and how this channel plays a role in intra- and extracellular pH regulation. In addition, the clinical relevance and potential contribution of TRPV6 to therapy resistance are discussed. Finally, we review pharmacological strategies and future perspectives regarding TRPV6 in PDAC. Full article

Melanoma adjuvant therapy has substantially improved recurrence-free and distant metastasis-free survival in patients with resected high-risk disease, and more recently, these advances have extended to earlier stages. However, important unmet needs remain, including the management of stage IIIA disease, the optimal treatment strategy after relapse on adjuvant therapy, and the identification of biomarkers capable of refining patient selection. This review summarizes recent advances and unresolved questions in the adjuvant and neoadjuvant treatment of melanoma. We discuss novel systemic strategies, including immune checkpoint inhibitor combinations and personalized neoantigen mRNA vaccines, together with the expanding role of neoadjuvant approaches. We also examine prognostic and predictive tools—such as clinicopathologic models, circulating tumor DNA, serum biomarkers, tumor microenvironment features, and gene expression profiling—that may help better define recurrence risk and therapeutic benefit. Current evidence suggests that although modern therapies have changed the natural history of resected melanoma, a substantial proportion of patients are still overtreated or undertreated when treatment decisions are based on stage alone. Future progress will depend on integrating biological risk stratification with clinical staging and optimizing treatment sequencing across adjuvant and neoadjuvant settings. Full article

Background: Colorectal cancer (CRC) represents a major global health burden, accounting for roughly 10% of all newly diagnosed cancers and cancer-related deaths worldwide. According to the World Health Organization, it is the third most diagnosed malignancy and the second leading cause of cancer mortality. Postoperative complications remain a significant concern after CRC resection, occurring in up to 50% of patients and contributing to increased morbidity, mortality, prolonged hospitalization, and substantial healthcare expenditure. Artificial intelligence (AI) has emerged as a transformative tool in modern healthcare, offering advanced capabilities in predictive analytics, clinical decision support, and personalized perioperative management. Methods: This review systematically evaluates the application of AI, specifically machine learning (ML) and deep learning (DL) algorithms, in the prediction of anastomotic leak (AL) and other major postoperative complications. In this context, AI models are generally used to refine risk stratification and enhance surgical decision-making. Results: A total of 13 studies were included, encompassing 15,105 patients. Across these studies, ML and DL algorithms consistently outperformed conventional statistical models in forecasting postoperative outcomes. Conclussions: Current evidence suggests that AI has substantial potential to improve perioperative risk prediction, support intraoperative decision-making, and personalize postoperative surveillance in patients undergoing CRC surgery. Methodological limitations, including a high risk of bias, limited external validation, heterogeneous outcome definitions, and inconsistent reporting, necessitate more robust, prospective, multicenter research before widespread clinical adoption can be realized. Full article

Background/Objectives: The aim of this study was to develop and validate a robust, radiomics-based classification model that uses pre-treatment MRI to non-invasively differentiate among major soft tissue sarcoma (STS) subtypes and a benign mimic. Methods: In this retrospective study, a cohort of 332 patients with biopsy-proven leiomyosarcoma, myxofibrosarcoma, myxoid liposarcoma, dedifferentiated liposarcoma, and undifferentiated pleomorphic sarcoma, along with the benign mimic intramuscular myxoma, was analyzed. Pre-treatment T1-weighted fat-saturated contrast-enhanced and T2-weighted fat-saturated MRI sequences were used for analysis. Following manual tumor segmentation, 1240 three-dimensional radiomic features were extracted. An XGBoost classifier was trained and validated using a robust 250-iteration bootstrap framework with nested cross-validation to ensure rigorous feature selection and unbiased performance evaluation. The model’s performance was assessed independently on T1-only, T2-only, and combined T1+T2 feature sets. Results: The combined T1 and T2 model achieved superior performance with an accuracy of 0.68 ± 0.04 and an AUC of 0.92 ± 0.02. At the subtype level, balanced accuracy was highest for intramuscular myxoma (0.91 ± 0.05), dedifferentiated liposarcoma (0.84 ± 0.06), and leiomyosarcoma (0.83 ± 0.05). SHAP analysis identified key features driving predictions, such as low T2 GLSZM Zone Size Entropy for myxoma and high T2 GLSZM Gray-Level Variance for leiomyosarcoma, which aligns with known pathological characteristics. Misclassifications predominantly occurred between subtypes with overlapping radiomic profiles. Conclusions: Radiomics applied to pre-treatment MRI enables robust, non-invasive classification of STS subtypes, demonstrating strong clinical potential for improving diagnostic confidence and informing triage strategies. Full article

The objective of this review is to evaluate the role of combined endobronchial and esophageal endosonography in mediastinal staging and to define its clinical implications within the proposed IASLC TNM 9th edition framework. Mediastinal staging remains a critical step in the management of non-small cell lung cancer (NSCLC), as it directly impacts treatment planning, surgical decision-making, and overall prognosis. For many years, mediastinoscopy was considered the standard approach; however, in routine practice, it has largely been replaced by less invasive techniques. Endobronchial Ultrasound (EBUS) and Endoscopic Ultrasound (EUS) have become widely adopted because they allow real-time sampling of lymph nodes with good accuracy and a low complication rate. In clinical settings, these techniques are often used together rather than separately, as each provides access to different nodal stations. This combined approach improves diagnostic yield and reduces the number of patients who require surgical staging. At the same time, recent updates in the IASLC TNM classification, including the proposed 9th edition, have introduced more detailed nodal categories, making accurate tissue confirmation even more important in daily practice. In this review, we summarize the current use of combined EBUS and EUS in mediastinal staging, focusing on their practical advantages, limitations, and roles across different clinical scenarios. We also discuss their relevance in the context of molecular testing and evolving treatment strategies. Despite their strengths, there are situations in which negative results should be interpreted with caution and confirmed surgically. Overall, these techniques have reshaped the approach to mediastinal staging and are now central to modern lung cancer care. Full article

Background: Relapse is the leading cause of treatment failure in patients with myeloid hematologic malignancies undergoing allogeneic hematopoietic cell transplantation. Clonal genomic evolution may contribute to post-transplant relapse, yet its determinants and prognostic impact remain incompletely characterized. Methods: In this retrospective study, we analyzed 63 patients with myeloid neoplasms who underwent cytogenetic evaluation both at diagnosis and at relapse after allogeneic hematopoietic stem cell transplantation. Cytogenetic changes (CGE), including evolution, devolution, or combined patterns, were assessed and correlated with clinical characteristics, prior treatment exposure, and survival outcomes. Results: Cytogenetic changes were observed in 46.1% of patients. The presence of cytogenetic changes (CGE) was strongly associated with the presence and complexity of cytogenetic abnormalities at initial diagnosis, whereas prior chemotherapy exposure, conditioning intensity, and donor type showed no significant association. Patients with cytogenetic changes had a lower complete remission rate at day 30 after transplantation; however, relapse-free survival and post-relapse survival did not differ significantly between groups. Conclusions: These findings suggest a potential association between post-transplant cytogenetic changes and intrinsic genomic instability, although treatment-related effects cannot be excluded. Larger, disease-stratified studies integrating cytogenetic and molecular analyses are warranted to further clarify the biological and prognostic relevance of clonal evolution following transplantation. Full article

Metastatic pancreatic ductal adenocarcinoma (PDAC) is typically treated with fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) or gemcitabine plus nab-paclitaxel (GnP), but the choice between regimens remains largely empirical. This narrative review summarizes biomarkers with potential to inform first-line selection in metastatic PDAC, emphasizing genomic and transcriptomic correlates of differential benefit. Recent head-to-head trials, particularly Pancreatic Adenocarcinoma Signature Stratification for Treatment (PASS-01) and GENERATE (Japan Clinical Oncology Group [JCOG] 1611), indicate that modified FOLFIRINOX (mFOLFIRINOX) is not uniformly superior to GnP, strengthening the rationale for biomarker-guided selection. The strongest evidence favoring platinum-based/FOLFIRINOX strategies involves homologous recombination repair deficiency (HRD), especially alterations in germline breast cancer gene 1/2 (BRCA1/2) or partner and localizer of BRCA2 (PALB2), as well as broader genomic scar signatures. Transcriptomic subtype and GATA-binding protein 6 (GATA6) expression are promising but remain unsettled because retrospective data favor classical/GATA6-high disease for FOLFIRINOX, whereas PASS-01 suggested better outcomes with GnP in classical tumors. Candidate biomarkers favoring GnP include high human equilibrative nucleoside transporter 1 (hENT1), low class III β-tubulin (TUBB3) expression, and exploratory phosphatidylinositol 3-kinase (PI3K)/KIT/NOTCH pathway mutation signals. Comprehensive molecular profiling also identifies actionable alterations that may redirect patients to targeted therapy or clinical trials rather than standard chemotherapy alone. Importantly, no biomarker has yet been prospectively validated in a biomarker-stratified randomized trial with regimen selection as the primary endpoint; all biomarker-regimen associations described in this review should therefore be considered hypothesis-generating rather than practice-defining. Nevertheless, the convergence of genomic, transcriptomic, and organoid-based approaches makes biologically informed first-line selection increasingly feasible in metastatic PDAC. Full article

Background. Preoperative risk stratification of pancreatic neuroendocrine tumors (PNETs) is constrained by the unavailability of histologic grade before resection. We hypothesized that a panel of biologically informed CT-radiomic signatures, combined with patient-level Δ-radiomics referenced to the contralateral pancreas, would support preoperative discrimination of progression and grade in a two-center pilot cohort. Methods. Forty-four patients with histologically confirmed PNET who underwent contrast-enhanced preoperative CT and surgical resection at two academic centers were analyzed. Lesion and contralateral non-tumor-bearing pancreatic parenchyma regions of interest were revised in 3D Slicer by a board-certified pancreatic surgeon and verified intraoperatively against surgical pathology. PyRadiomics v3.0 features were extracted with IBSI-concordant settings. Parametric ComBat batch correction was applied across the two centers (biological-covariate balance verified beforehand), and Δ-radiomic features (lesion combat–pancreas combat) were computed for the 106 intensity/texture primitives. We constructed a panel of biology-informed hybrid signatures partitioned into a preoperative lesion-only family (Family A; seven signatures) and a preoperative Δ-radiomic family (Family B; three signatures). Candidate features were filtered through correlation clustering, baseline-adjusted likelihood-ratio testing with Benjamini–Hochberg FDR control, and 100-bootstrap stability selection. Three predictor blocks were compared per target with three classifiers each (Logistic Regression, Random Forest, Gradient Boosting): M0 (five-variable clinical baseline), MA (M0 + Family A), and MB (M0 + Family B). Discrimination was reported as AUC with bootstrap 95% CI; calibration was assessed using the Brier score and TRIPOD-recommended calibration intercept and slope; and cross-center generalization was evaluated with leave-one-center-out (LOCO) cross-validation. Univariable Cox regression with bootstrap and permutation inference was used for progression-free survival (PFS). Results. The cohort had 16 progression events and eight deaths (median follow-up was 38 months, IQR 14–59). Prespecified clinical–radiomic and Δ-radiomic signatures were associated with progression-free survival, including B2 = ΔBusyness × Ki-67 (HR 0.38, 95% CI 0.19–0.76, p = 0.006). For progression prediction, the Δ-radiomic model achieved the strongest discrimination, with a nested cross-validation AUC of 0.85 and leave-one-center-out AUC of 0.87. For higher-grade disease, radiomic models also demonstrated high discrimination, with AUCs up to 0.93. Conclusions. Radiomics-derived shape and texture features, especially when combined with clinical markers, may noninvasively identify aggressive PNET phenotypes and support preoperative risk stratification. Prospective validation in larger multicenter cohorts is warranted. Full article

Molecular testing has become an increasingly important adjunct in the evaluation of cytologically indeterminate thyroid nodules. These tests analyze genetic alterations associated with thyroid tumorigenesis, including point mutations, gene fusions, and gene expression profiles, with the aim of refining preoperative risk assessment and reducing unnecessary diagnostic surgery. Despite these advances, the clinical utility of molecular testing remains highly dependent on the context in which results are interpreted. Molecular alterations do not consistently correlate with tumor aggressiveness, and several mutations are observed in both benign and malignant thyroid lesions. In addition, the predictive performance of molecular tests is strongly influenced by the baseline prevalence of malignancy, which varies across clinical settings and is shaped by diagnostic thresholds and patient selection. This commentary summarizes the molecular landscape of thyroid tumors, the diagnostic performance of current molecular testing platforms, and their role in clinical decision-making. Emphasis is placed on the interpretation of molecular findings within a broader diagnostic framework that incorporates cytologic morphology, ultrasound-based risk stratification, and clinical context. A selective, risk-adapted approach to molecular testing may provide the most effective strategy for optimizing patient management while minimizing unnecessary intervention. Full article

Background: Human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) generally has a more favorable prognosis compared to HPV-negative cases. Overexpression of p16^INK4a is widely used as a surrogate marker for HPV-induced carcinogenesis, and it also represents an important tumor suppressor gene, the second most frequently altered after TP53. In turn, mutations in TP53 are characteristic of tumors linked to smoking and alcohol consumption and p53 expression is consistently associated with worse clinical outcomes. Aims: Investigate the impact of p53 immunohistochemical expression on prognosis of OPSCC. Methods: This retrospective study included 155 OPSCC patients with longitudinal follow-up exceeding 10 years. Immunohistochemistry was used to evaluate p53 protein expression. Clinicopathological associations were performed to evaluate the prognostic impact of p53 protein expression in OPSCC HPV-positive and HPV-negative tumors. Results: Among the 155 OPSCC cases, 90 (58.1%) were classified as HPV-positive and 65 (41.9%) as HPV-negative. HPV status was inversely associated with p53 positivity, with HPV-negative tumors showing a higher frequency of p53 expression (p < 0.0001). Patients with HPV-positive tumors experienced better clinical outcomes than those with HPV-negative disease, including cancer-specific survival (CSS; HR: 3.47, 95% CI 1.16–10.4, p = 0.02) and disease-free survival (DFS; HR: 3.73, 95% CI 1.29–10.7, p = 0.01), whereas p53 positivity alone was not independently associated with survival. Notably, individuals with HPV-negative and p53-positive tumors exhibited the poorest outcomes, in contrast to patients with HPV-positive OPSCC, regardless of p53 expression. Conclusions: Patients with HPV-negative and p53-positive OPSCC showed inferior clinical outcomes compared with their HPV-positive counterparts, independent of p53 status. These findings underscore the prognostic relevance of jointly evaluating HPV status and p53 expression in OPSCC and support more refined risk stratification and personalized therapeutic strategies. Full article

Background: Her-2 positive breast cancer is characterised by a high risk of metastases to the central nervous system, which significantly affects prognosis. The aim of this study was to analyse risk factors and treatment outcomes for brain metastases diagnosed at the time of first progression. Materials and Methods: A retrospective analysis was conducted on 1226 patients treated between 2010 and 2022. Distant metastases were diagnosed in 186 (15.7%) patients, including 48 (25.8%) with BM at the time of first progression. The impact of clinical factors and treatment on overall survival (OS) and intracranial progression-free survival (PFS) was analysed. Results: Patients with BM were significantly younger than other patients with distant metastases (mean 52.4 years vs. 61.1 years, p = 0.0001). The most significant prognostic factor for OS was the number of intracranial lesions (p = 0.0004). OS did not differ significantly depending on the use of local therapy (local therapy vs. whole-brain radiotherapy) or systemic therapy (observation vs. chemotherapy vs. anti-Her2 treatment). Conclusions: The number of brain metastases remains a key prognostic factor and should be taken into account in therapeutic decision-making, which highlights the importance of early identification of high-risk patients and the number of intracranial lesions in treatment selection. Full article

Background/Objectives: Gliomas are among the most aggressive primary brain tumors in adults, characterized by profound molecular heterogeneity and poor response to conventional therapies. Immunotherapy has transformed outcomes in several cancers, yet glioma remains largely refractory, due in part to an immunosuppressive tumor microenvironment. Post-transcriptional regulation of gene expression is increasingly recognized as a key mechanism controlling immune cell function in tumors. Regnase-1, an endoribonuclease regulating the stability of inflammation- and immunity-related mRNAs, is a central modulator of immune responses; however, its role in glioma progression and immune modulation remains poorly understood. This study aimed to evaluate Regnase-1 expression in glioma and investigate its association with tumor grade, prognosis, and immune microenvironment characteristics. Methods: Regnase-1 transcript levels were evaluated by RT-PCR in tumor samples from 40 Moroccan glioma patients and validated using transcriptomic data from The Cancer Genome Atlas (TCGA, n = 672) and the Chinese Glioma Genome Atlas (CGGA, n = 959). Bioinformatic analyses and statistical assessments were performed using established pipelines. Results: Regnase-1 expression was significantly elevated in glioblastoma, IDH-wildtype tumors, and higher tumor grades, correlating with poorer overall survival, and emerging as an independent prognostic factor in the CGGA cohort. High Regnase-1 expression was associated with enrichment of pathways related to angiogenesis, hypoxia, invasion, and immune evasion. Tumors with elevated Regnase-1 showed reduced infiltration of effector immune cells (CD8⁺ T cells, Th1 cells) and increased presence of immunosuppressive populations, including regulatory T cells, myeloid-derived suppressor cells, and M2 macrophages. Single-cell analyses further highlighted exhausted CD8⁺ T cells and regulatory T cells as major populations linked to Regnase-1 expression. Notably, Regnase-1 expression also exhibited strong positive correlations with multiple inhibitory immune checkpoint pathways. Conclusions: Elevated Regnase-1 expression defines an aggressive, immunosuppressive glioma phenotype and is associated with poor prognosis, supporting its potential as a prognostic biomarker and a target for immunomodulatory strategies. Full article

Diabetes mellitus (DM), particularly Type 2 DM (T2DM), is increasingly recognized as both a risk factor and an early manifestation of pancreatic ductal adenocarcinoma (PDAC), yet the molecular mechanisms bridging these conditions remain poorly understood. There is growing evidence that chronic metabolic stress in diabetes induces persistent cellular reprogramming and metabolic memory through stable post-translational and epigenetic alterations, independent of conventional insulin resistance, obesity, and inflammatory pathways. We aim to elucidate how hyperglycaemia and metabolic overload contribute to the accumulation of major intermediates, such as acetyl-CoA, Uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), and reactive oxygen species, which induce broad changes in post-translational modifications in diabetes-induced PDAC. A comprehensive literature search was conducted using electronic databases, including PubMed, Scopus, and Web of Science databases, to retrieve studies published between 2005 and 2025. This review synthesizes current understanding of post-translational modifications (PTM) dynamics in diabetes-associated PDAC, with emphasis on their role in modulating oncogenic pathways such as KRAS-MAPK and PI3K-AKT. We introduce the concept of PTM remodeling, wherein transient metabolic perturbations become persistently stabilized, contributing to metabolic memory and tumor initiation. In addition, we examine how PTM-driven alterations influence the pancreatic tumor microenvironment, including stromal activation, immune evasion, and metabolic crosstalk, reinforcing a bidirectional link between tumor progression and systemic metabolic dysfunction. Furthermore, emerging therapeutic strategies targeting PTM-regulating enzymes, metabolic substrates, and signaling nodes are discussed as potential approaches to disrupt this axis. Collectively, precision targeting of PTM-mediated metabolic reprogramming represents a promising framework for early intervention and therapeutic development in PDAC associated with diabetes. Full article

Background: Since the advent of imatinib, more potent next-generation tyrosine kinase inhibitors (TKIs) and asciminib have expanded therapeutic options for chronic myeloid leukemia (CML). Treatment-free remission (TFR) is an important goal in CML management, but only ~30% of patients can achieve it, leaving many on lifelong therapy. TKIs are usually used in escalating order of potency, but in patients ineligible for or failing TFR, “downgrading” to safer, lower-potency agents may be advantageous. Methods: We analyzed this strategy in 157 patients across 29 Italian CML Campus centres. Data were collected via e-forms in July 2024. Prognostic scores at diagnosis did not influence downgrading. Results: The most downgraded TKIs were nilotinib (47%) and dasatinib (37%). Imatinib was the most frequent target agent (69.7%), followed by nilotinib and bosutinib. The majority underwent downgrading during first-line therapy and most after prior dose de-escalation. Adverse events were the leading reason for downgrading (79%). Notably, in 52.6% of cases, molecular responses improved afterwards. Twenty-one patients subsequently attempted TFR, with 17 (81%) remaining treatment-free at a median follow-up of 22 months. Conclusions: These results show that, beyond the known role of de-escalation, downgrading represents a new, feasible approach to maintaining long-term control, limiting toxicity and costs, and favouring TFR. Full article

Juvenile myelomonocytic leukemia (JMML) is a rare, aggressive myeloproliferative neoplasm of early childhood characterized by constitutive activation of the RAS-MAPK signaling pathway. RASopathies are a heterogeneous group of complex genetic disorders arising from germline mutations that dysregulate RAS-MAPK signaling. Noonan syndrome, CBL syndrome, and neurofibromatosis type 1 (NF1) are the three major RASopathies predisposing to JMML. More than 90% of JMML cases harbor germline or somatic mutations in one of five canonical driver genes—PTPN11, NRAS, KRAS, NF1, or CBL—establishing JMML as the prototypical malignant manifestation of RASopathy biology. The fifth edition of the World Health Organization Classification of Tumours reclassified JMML as a myeloproliferative neoplasm while the International Consensus Classification adopted JMML under pediatric and/or germline mutation-associated disorders, introducing a JMML-like category for cases lacking five canonical mutations but harboring emerging drivers such as SH2B3::LNK alterations and ALK::ROS1 fusions. The distinction between germline and somatic mutations profoundly influences prognosis: e.g., germline PTPN11-associated myeloproliferations and many germline CBL cases undergo spontaneous resolution, whereas somatic PTPN11- and NF1-mutated JMML is more aggressive and requires prompt allogeneic hematopoietic stem cell transplantation. DNA methylation profiling has emerged as the most robust prognostic framework, with consensus defining high-, intermediate-, and low-methylation subgroups that independently predict outcome. Both genotype and DNA methylation subclassification have been integrated into clinical decision-making, incorporating pretransplant azacitidine, watch-and-wait approaches for favorable-risk patients, and emerging targeted therapies including MEK inhibitors. This review synthesizes recent advances in understanding JMML as a bona fide RASopathy; provides a diagnostic algorithm, molecular landscapes, and prognostic models; and highlights opportunities for molecularly targeted therapeutic intervention. Full article

Focused ultrasound (FUS)-mediated therapies have evolved with the advent of modern ultrasound-guided technology and MRI imaging, moving from their initial use as thermal ablation to a multifunctional platform for thermal and non-thermal ablation, immunomodulation, and targeted drug delivery. This narrative review explores the potential, limitations, and challenges of ablative high-intensity focused ultrasound (HIFU) therapies: HIFU thermal ablation and non-thermal ablation, histotripsy, as well as non-ablative low-intensity focused ultrasound (LIFU) applications in the management of hepatobiliary cancers. HIFU and histotripsy are reviewed as alternative or complementary treatment options in liver tumors, as well as their potential as bridging therapy. Histotripsy is addressed as a theranostic tool, not only by combining ablation with real-time ultrasound imaging guidance, but also by integrating it with sonobiopsy. It facilitates a liquid sonobiopsy of the ablated tumor by releasing intact tumor antigens and damage-associated molecular patterns, leading to potential molecular profiling. LIFU-induced targeted drug delivery (sono-chemotherapy), sonodynamic therapy, radiosensitization, immunomodulation of the immunosuppressive tumor microenvironment (sono-immunotherapy), and the potential to enhance the effect of immune checkpoint inhibitors in these malignancies are discussed. Since FUS-assisted procedures exhibit dual actions through therapeutic functionality associated with intra- and post-procedural ultrasound imaging guidance, they could have value as a theranostic tool in hepatobiliary interventional oncology. Although promising, the available clinical evidence for FUS-mediated therapies in hepatobiliary malignancies consists predominantly of early-stage feasibility studies, retrospective observational cohorts, and non-randomized comparative analyses. Further studies focused on standardized protocols, validation through large-scale, multicenter, prospective randomized clinical trials comparing FUS-based therapies with established treatments, and long-term follow-up of oncological efficacy could define their future role in multimodal oncological strategies. Full article

Background: The clinical significance of lymphatic invasion in mucosal early gastric cancer (EGC) treated with endoscopic submucosal dissection (ESD) remains unclear. We evaluated clinicopathologic features and long-term outcomes in patients with lymphatic invasion as the sole non-curative factor. Methods: We retrospectively reviewed 9117 patients who underwent ESD for EGC at Samsung Medical Center between 2001 and 2022. Among patients with mucosal disease and lymphatic invasion as the sole non-curative factor, long-term clinical outcomes were summarized using an outcome flowchart, and characteristics of lymph node-positive cases were analyzed in relation to curative resection criteria. Results: Among 7444 patients with mucosal EGC treated with ESD, lymphatic invasion was identified in 154 patients (2.1%). Among the 117 patients with lymphatic invasion as the sole non-curative factor, the overall rate of pathologically confirmed or clinically suspected lymph node metastasis (LNM) was 4.3% (5/117). Specifically, LNM was identified in 3.2% (3/95) of patients who underwent additional surgery, and in 9.0% (2/22, including one clinically suspected case) managed with observation alone during a median follow-up of 58.0 months. LNM was observed exclusively in lesions involving the muscularis mucosae or in lesions larger than 2 cm, whereas no LNM occurred in tumors confined to the lamina propria measuring ≤ 2 cm. Conclusions: Despite mucosal confinement, lymphatic invasion was associated with a clinically meaningful risk of LNM, whereas no LNM was observed in lesions ≤ 2 cm confined to the lamina propria. For patients with mucosal EGC in whom lymphatic invasion is the sole non-curative factor, careful, individualized decision-making is warranted. Full article

Background: Gliomas are characterized by a high degree of molecular heterogeneity, which impairs the reproducibility of predictive biomarkers derived from bulk-based molecular profiling due to immune/stromal contamination of tumors and the high prevalence of the IDH mutation signature. Methods: In this study, we used MOFA+ to derive intrinsic molecular signatures from transcriptional, methylation, and genomic profiles of a cohort of 667 diffuse gliomas in the Cancer Genome Atlas database. Thereafter, factor scores were derived for two separate Chinese Glioma Genome Atlas batches (Batch 1, n = 325; Batch 2, n = 693) without any retraining on the model. The prognostic independence of identified molecular signatures was assessed using multivariable Cox regression adjusted for IDH mutation status and tumor purity; purity-residualized survival analyses; IDH-stratified Cox regression in each cohort; validation by concordance index against established molecular signatures; and survival extreme profiling. To characterize the biological significance of factor signatures, we projected gene set signatures corresponding to each factor signature onto a single-cell RNA-seq dataset of GBM (GSE131928). Results: MOFA+ identified 12 latent factors, of which a vascular–extracellular matrix (ECM) remodeling axis (Factor 1) explained the highest multi-omics variance (24.9%) and was the strongest independent prognostic factor. In multivariable Cox regression adjusting for IDH status and tumor purity, Factor 1 remained independently prognostic (HR = 1.67, 95% CI 1.27–2.20, p = 0.0002); in a fully-adjusted model additionally including age, WHO grade, MGMT methylation, and 1p/19q codeletion (plus radiotherapy and chemotherapy status in the CGGA cohorts), Factor 1 remained prognostic in both CGGA cohorts (CGGA1: HR = 1.50, p = 3.8 × 10⁻⁵; CGGA2: HR = 1.18, p = 0.003) but lost significance in TCGA (HR = 1.04, p = 0.83), consistent with the cohort-dependent magnitude reported in the IDH-stratified and meta-regression analyses below. Purity-residualized survival analysis showed negligible attenuation of the Factor 1 signal (raw HR = 3.57 vs. residualized HR = 3.72; concordance 96.5%). Within IDH-wildtype gliomas, Factor 1 was significant in both external validation cohorts (CGGA1: HR = 1.64, FDR = 4.6 × 10⁻⁶; CGGA2: HR = 1.20, FDR = 0.02), though the TCGA IDH-wildtype subgroup showed a trend that did not survive FDR correction (FDR = 0.060). All validation was performed without model retraining. Within IDH-mutant gliomas, Factor 1 was strongly prognostic in both CGGA cohorts but was not significant in TCGA (HR = 1.17, FDR = 0.33). These findings should therefore be interpreted as consistent in directionality across cohorts but not uniformly replicated at the FDR-adjusted significance threshold in the TCGA discovery dataset. Concordance index benchmarking on a matched subset (n = 503) showed Factor 1 achieved discrimination comparable to the Mesenchymal signature (C = 0.797 vs. 0.801; ΔC = −0.004) while outperforming four other established classifiers. Factor 1 consistently separated patients with extreme survival phenotypes (OS < 6 vs. >15 months) across all three cohorts (all log-rank p < 0.001). Projection onto a single-cell GBM atlas (GSE131928), supported by inferCNV-based malignant-cell classification, localized the Vascular–ECM program to malignant cells and the Immune–ECM axis to myeloid compartments. Conclusions: The Vascular–ECM axis is a consistent, prognostic program robust to purity adjustment for diffuse gliomas that remains relevant across IDH-defined subgroups in three independent datasets comprising 1685 patients. The Vascular–ECM axis is a reproducible, purity-robust prognostic program in diffuse glioma, with directionally consistent adverse effects across TCGA, CGGA Batch 1, and CGGA Batch 2 (pooled n = 1685). Given the strong co-loading of endothelial, ECM, and myeloid genes observed in the single-cell projection, Factor 1 is best interpreted as a vascular/ECM-associated tumor–microenvironment ecosystem program rather than a malignant-cell-autonomous signature. Its FDR-adjusted significance within IDH-stratified subgroups is cohort-dependent and robust in both CGGA cohorts but attenuated in the TCGA IDH-wildtype (FDR = 0.060) and TCGA IDH-mutant (FDR = 0.33) strata. The pooled signal should therefore be interpreted as evidence of a generalizable biological program rather than a uniformly replicated subgroup-specific biomarker. It is possible to calculate factor scores based on RNA sequencing alone using fixed loadings (Z = XWᵀ), which may have implications for future translational applications. All findings are correlative; a causal role for the Vascular–ECM program in glioma progression, invasion, or therapy resistance remains to be established through functional perturbation experiments. Full article

Upper tract urothelial carcinoma (UTUC) presents distinct diagnostic and therapeutic challenges because of its rarity, anatomic constraints, frequent understaging at biopsy, and risk of systemic recurrence after radical nephroureterectomy. Current perioperative management is driven primarily by clinicopathologic risk factors, which may be insufficient to identify occult molecular residual disease (MRD) or to determine which patients are most likely to benefit from systemic therapy. This narrative review summarizes available evidence on circulating tumor DNA (ctDNA) in UTUC and related urothelial carcinoma settings, classifies the level of evidence supporting each application, and proposes a research framework for prospective evaluation. The strongest UTUC-specific evidence supports ctDNA as a prognostic biomarker associated with recurrence risk, whereas predictive validity for selecting chemotherapy, immune checkpoint inhibitors, antibody-drug conjugates, targeted therapy, or surveillance intensity remains unproven. Evidence from muscle-invasive bladder cancer, including ctDNA-correlative and ctDNA-guided perioperative trials, provides biologic rationale but should not be directly translated into routine UTUC care without disease-specific validation. We outline key implementation questions, including target population, assay selection, timing, false-positive and false-negative results, lead-time bias, and integration of plasma ctDNA with utDNA. Prospective UTUC-specific trials are needed to determine whether ctDNA-guided perioperative strategies improve survival, reduce unnecessary toxicity, and are cost-effective. Full article

Background: Surveillance of non-muscle-invasive bladder cancer (NMIBC) relies on cystoscopy and urine cytology, both of which have well-recognised limitations. Molecular urine assays have been developed to reduce the burden of invasive surveillance, yet their real-world clinical utility remains uncertain. Uromonitor^® is a quantitative PCR-based assay targeting hotspot variants in the TERT promoter, FGFR3, and KRAS, which are frequently altered in urothelial carcinoma. We evaluated the performance of Uromonitor^® in routine clinical practice and assessed its technical reproducibility. Methods: Uromonitor^® diagnostic test accuracy was retrospectively calculated from samples from patients undergoing investigation for suspected bladder cancer (n = 64) or surveillance (n = 30) following a prior diagnosis at a tertiary referral centre between 2021 and 2023. Uromonitor^® results were compared with histology where available (n = 49, 52%), or with contemporaneous cystoscopy and urine cytology findings (n = 45, 48%). This pragmatic dual reference standard reflects routine clinical practice but may introduce some heterogeneity in diagnostic accuracy verification. A prospective in-house verification cohort was used to assess inter-laboratory reproducibility. Discordant cases underwent orthogonal next-generation sequencing (NGS) analysis. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were calculated for the Uromonitor^® against the standard of care. Results: Ninety-four patients were included in the clinical performance analysis. Overall sensitivity, specificity, PPV, NPV and overall accuracy for Uromonitor^® were 38%, 88%, 63%, 72% and 70%, respectively. Sensitivity was higher in the diagnostic setting (47%; 95% CI 27.3–68.3%) than during surveillance (23%; 95% CI 8.2–50.2%). Several false-negative cases in the verification cohort harboured variants either detectable by NGS at variant allele frequencies below or slightly above the assay’s limit of detection or variants not covered by the assay hotspot design. Inter-laboratory reproducibility was excellent, with 100% concordance observed in the verification cohort. Conclusions: In a real-world clinical setting, Uromonitor^® demonstrated high specificity but limited sensitivity for detection of bladder cancer, particularly during surveillance. A negative result does not reliably exclude recurrence. Assay sensitivity thresholds and restricted variant coverage appear to be key contributors to false-negative results. These findings highlight the need for cautious clinical integration of Uromonitor^®. It is unclear whether this approach has sufficient sensitivity in surveillance to safely reduce cystoscopy frequency. This underscores the need for further refinement of urine-based molecular assays, including a need for enhanced sensitivity and broader mutational coverage before routine clinical adoption. Full article

Introduction: Giant retroperitoneal liposarcomas (GRPLs) are rare tumors that often reach considerable size before diagnosis due to their indolent growth and deep anatomical location. Surgery represents the only potentially curative treatment, yet recurrence rates remain high. While histological subtype is a recognized predictor of recurrence, the prognostic role of tumor size, particularly in giant tumors, remains controversial. This study evaluates the impact of tumor size and histological subtype on recurrence risk in a literature-based retrospective cohort. Materials and Methods: Data were extracted from a literature-based database of GRLPs published between 2004 and 2023. Only tumors >20 cm treated without positive surgical margins were included; patients receiving adjuvant therapy or with missing follow-up were excluded. Histological subtype (well-differentiated vs. other) was the main variable of interest. Recurrence-free survival (RFS) was defined as the primary endpoint and estimated using the Kaplan–Meier method. The association between histological subtype and recurrence risk was evaluated using a Cox proportional hazards model. A sensitivity analysis was performed to explore the potential interaction between tumor size and histological subtype. Results: Our final cohort yielded a total of 81 patients, of whom 47 (58%) had a well-differentiated GRLPs. The median tumor size was 38 cm and median follow-up was 16 months, with 24 recurrences observed. At 24 months, RFS was higher in well-differentiated tumors than in other histological subtypes (81% vs. 41%). In multivariable Cox analysis, histology was independently associated with recurrence risk (HR 3.2, 95% CI 1.28–8.17, p = 0.01), whereas tumor size showed no association with recurrence. Interaction analysis confirmed no differential effect of tumor size across histological subtypes. Conclusions: In this literature-based cohort of GRLPs treated with surgery, histological subtype independently predicted recurrence, whereas tumor size showed no prognostic value, either overall or within individual histological subtypes. Full article

Background: Human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) differs from HPV-negative OPSCC in its molecular, biological, and clinical characteristics. We reviewed the literature on radiological differences between HPV-positive and HPV-negative OPSCC across ultrasound, CT, MRI, and PET-CT as this appears to be a critical gap in the literature. Methods: We performed a narrative review of studies reporting imaging findings in OPSCC by HPV status. Two reviewers independently searched PubMed, Ovid MEDLINE, Ovid EMBASE, and the Cochrane Library, from inception to February 2026, supplemented by searching major radiology journals and the grey literature. Eligible English-language studies included patients with OPSCC of known HPV status, assessed at least one imaging modality, and reported imaging findings stratified by HPV status. After title, abstract, and full-text screening, 66 studies were included. Results: HPV(+) OPSCC was more commonly associated with well-defined primary tumours and a higher prevalence of nodal metastases, particularly cystic nodal metastases and extranodal extension. These findings were broadly concordant with reported radiomic signatures. MRI studies suggested lower apparent diffusion coefficient values, while PET-CT studies suggested higher entropy and smaller primary lesions in HPV-positive disease. Conclusions: Selected imaging features may help distinguish HPV(+) from HPV(−) OPSCC, but current evidence remains insufficient for reliable standalone clinical application. Prospective multicentre validation and integration of multimodal imaging, radiomics, and radiogenomics are needed to improve non-invasive HPV stratification and support future precision diagnostics. Full article

Background: Long-term survivors (LTS) after gynecological cancer may be cured but still face physical and psychological challenges. This multicenter study aimed to assess the long-term side effects, the received follow-up care, and the personal perspectives of survivors. Methods: Between 2019 and 2025, LTS from four European countries within the ENGOT (European Network of Gynecological Oncological Trial Groups) and GCIG (Gynecologic Cancer InterGroup) networks were recruited. Long-term survival was defined as surviving at least five years after the first diagnosis. LTS completed a questionnaire with 81 questions (patient’s characteristics, oncological history, current health status, lifestyle factors). Analyses were mainly descriptive. Results: A total of 677 LTS were enrolled, with a median age of 64.0 years (range: 26–92) and a median survival time of 7 years (range: 5–38). A total of 46.6% were diagnosed with cervical cancer, 32.9% with endometrial cancer, 4.4% with ovarian cancer, and 16.1% with other types of gynecological cancer. Moreover, 36.9% still suffer from physical and psychological symptoms, most frequently being lymphedema (36.2%), hot flashes (22.4%), difficulties with concentration (21.1%), fatigue (20.9%), vaginal dryness (20.1%), and urinary incontinence (18.9%). Median overall health status was ranked (scale 1–5; 1 = very good, 5 = very poor) as 2, while 13.5% rated their health as poor/very poor. Current symptoms were associated with poorer health status (p < 0.001) and a history of recurrent disease (p = 0.001). In addition, 13.6% reported not receiving follow-up care. CA-125 was determined in 80.8% of ovarian LTS, as well as in 30.7% of cervical and 28.9% of endometrial LTS. Pap smear follow-up was reported by 50.5% of endometrial LTS. A total of 33.7% did not exercise at all or exercised less than an hour per week, 13.4% smoke tobacco, and 51.2% drink alcohol more often than once a month. Conclusions: Our findings highlight the need for patient-centered follow-up care, addressing both long-term side effects and education on lifestyle and prevention. Follow-up procedures that do not follow guidelines should be avoided. Full article

Background/Objectives: Increasing evidence indicates that gliomas co-opt mechanisms of excitatory synaptic transmission and plasticity to support tumor progression, yet these processes remain poorly characterized in lower-grade gliomas (LGGs). Here, we investigated whether genes associated with excitatory synaptic function are linked to patient prognosis in LGG. Methods: A curated panel of 36 synaptic genes was analyzed in LGG using RNA-sequencing and clinical data from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) datasets. Results: Among the genes investigated, DLG2, DLG3, and DLG4, which encode the postsynaptic scaffolding proteins PSD-93, SAP-102, and PSD-95, respectively, showed strong associations with patient overall survival (OS). Higher expression of each gene was consistently associated with longer OS across both datasets. Expression of DLG2–DLG4 was higher in oligodendroglioma and IDH-mutant, 1p/19q co-deleted tumors, and lower in astrocytoma and IDH-wild-type tumors. Furthermore, expression of all three genes positively correlated with a broad gene signature associated with a synaptic gene program, including multiple components of glutamatergic signaling and postsynaptic organization. Conclusions: These findings suggest that elevated expression of DLG2–DLG4 is associated with a transcriptional program resembling differentiated neuron-like features and favorable clinical outcome in LGG. Full article