Search Results (5,598)

Background: Non-melanoma skin cancer (NMSC) is the most frequent cancer in fair-skinned populations and represents a growing public health concern due to its impact in terms of morbidity and treatment costs. While some meta-analyses have investigated cigarette smoking as a risk factor for NMSC, less is known about its prognostic implications in patients with NMSC. This systematic review and meta-analysis aims to fill this gap by assessing the association between smoking habits and survival in patients with NMSC. Methods: A systematic search was conducted in PubMed and EMBASE up to 25 February 2025, to identify prospective studies of patients with histologically confirmed NMSC that evaluated the association between smoking habits and survival. Study-specific hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were pooled using random effects meta-analysis models. Results: A total of five studies published between 2015 and 2022 were included. The meta-analysis revealed that being a current or ever smoker at diagnosis was associated with a worse overall survival (summary HR 2.42, 95% CI 1.91–3.06). A similar result was observed when smoking exposure was assessed in terms of pack-years or number of cigarettes per day (summary HR 2.44, 95% CI 2.02–2.93). Conclusions: Our findings indicate that cigarette smoking is a negative prognostic factor in these patients, despite the generally excellent prognosis of NMSC. It is reasonable to assume that this unfavourable effect is largely due to the increased risk of developing other life-threatening conditions, in which smoking plays a causal role. These results underscore the clinical relevance of systematically integrating smoking cessation counselling into the routine management of patients with NMSC. Full article

Background/Objectives: Metastatic bone disease (MBD) poses an increasing challenge in orthopaedic oncology due to prolonged survival. While clinical prognostic factors are well established, the role of socio-economic determinants remains unclear, particularly within universal healthcare systems. Methods: We retrospectively analysed 243 patients who underwent surgery for MBD (excluding spine) between 2005 and 2024 at a German sarcoma centre. Socio-economic indicators were derived from national databases and linked to patients’ residential districts. Survival was analysed using Kaplan–Meier estimates and Cox regression, adjusting for clinical confounders. Results: Median postoperative survival was 22 months. Several socio-economic indicators—income, education, and employment—were associated with survival in univariate analysis. In multivariate models, only residential area size remained independently significant (p = 0.047). Patients from villages (<2000 inhabitants) and large cities (>100,000) had poorer survival than those from small or medium-sized towns. This effect persisted after adjustment for tumour type, pathological fractures, and year of surgery. Conclusions: Within a universal healthcare system, residential area size was associated with survival after surgery for MBD, suggesting that regional disparities may persist despite equal formal access to care. Further studies integrating individual-level socioeconomic data are needed to identify mechanisms and guide interventions to reduce geographic inequalities. Full article

In recent decades, the novel role of Galectin-3 (Gal-3) in both physiological and pathological conditions has emerged. Gal-3 is a key protein involved in immunity, inflammation, cell adhesion, proliferation, differentiation, and apoptosis. Its physiological role is crucial for the regulation of these cellular functions. In pathological settings, elevated levels of Gal-3 are associated with diseases such as cancer, heart failure, and fibrotic diseases, making it an important diagnostic and prognostic biomarker in these conditions. It seems that Gal-3 acts as a bridge between different diseases. Because of its pro-inflammatory and pro-tumorigenic properties, it connects atherosclerosis and cancer, regulating inflammation, cell proliferation, immune evasion, angiogenesis and survival in both diseases. Specifically, in atherosclerosis, Gal-3 promotes plaque formation by driving inflammation, oxidative stress, lipid deposition, and vascular cell migration. In cancer, Gal-3 influences tumor growth and metastasis by modulating an immunosuppressive tumor microenvironment, increasing cell survival, and enhancing cell–matrix and cell–cell interactions. Moreover, by stimulating fibroblasts, Gal-3 favors matrix deposition and tissue fibrosis that together with the inflammatory properties contributes to adverse ventricular remodeling leading to heart failure. Finally, taking into account its role in pathogen recognition and immune cells (B and T cells) modulation, Gal-3 might be a critical factor in host defense, disease progression, and the development of autoimmune conditions. Thus, targeting Gal-3 might be a promising therapeutic strategy to pursue for management of different pathological scenarios. Full article

Background/Objectives: Moderate aortic stenosis (AS) with preserved ejection fraction (EF) is common, yet risk stratification remains challenging. Cardiopulmonary exercise testing (CPET) and myocardial mechanics analysis may identify subclinical dysfunction and impaired functional capacity. To evaluate the relationship between functional capacity (by % predicted peak VO₂), ventilatory efficiency (VE/VCO₂ slope), and myocardial mechanics (speckle tracking echocardiography—STE), and myocardial work (MW) indices) in moderate AS with preserved EF. Methods: We prospectively enrolled 107 patients with moderate AS (AVA 1.0–1.5 cm²; mean gradient 20–40 mmHg; EF ≥ 50%). Functional capacity was classified as preserved (≥83% predicted VO₂) or reduced (<83%). Ventilatory efficiency was defined as good (<30) or poor (≥30) VE/VCO₂ slope. STE assessed left ventricular (LV), left atrial (LA), and right ventricular (RV) strain, as well as myocardial work indices. Results: Patients with reduced % predicted VO₂ had higher LV end-systolic volume (p = 0.035), lower stroke volume index (p = 0.020), and smaller indexed aortic valve area (p = 0.025), with trends toward lower GLS and myocardial work. In contrast, patients with poor ventilatory efficiency (VE/VCO₂ ≥ 30) showed significant impairments in global longitudinal strain (GLS, p = 0.002), LA reservoir strain (PALS, p = 0.019) and LA conduit strain (LA Scd, p < 0.001), RV free wall strain (RW FWS, p = 0.029), and myocardial work indices (lower GWI and GCW, higher GWW, reduced GWE; all p < 0.05). LA Scd emerged as the strongest predictor of poor ventilatory efficiency. (receiver operating characteristic (ROC) area under the curve (AUC) 0.723, 95% confidence interval (CI) 0.623–0.823, p < 0.001). Conclusions: In moderate AS with preserved EF, impaired ventilatory efficiency is more strongly associated with subclinical LV, LA, and RV dysfunction than reduced % predicted VO₂, highlighting the key role of RV impairment. Integrating CPET and STE improves phenotyping, identifying high-risk patients who may benefit from closer surveillance or early intervention. These findings are exploratory and hypothesis-generating; longitudinal data are needed to confirm prognostic implications. Full article

Introduction: Breast cancer is a heterogeneous malignancy influenced by diverse molecular profiles. The L-type amino acid transporter 1 (LAT1), encoded by the SLC7A5 gene, plays a key role in tumor metabolism, growth, and angiogenesis. Through its role in amino acid transport and activation of the mTORC1 signaling pathway, LAT1 has emerged as a potential therapeutic target. Objective: To evaluate SLC7A5/LAT1 expression and its association with clinicopathological parameters and molecular subtypes of invasive carcinoma of no special type (NST) in a Pakistani cohort. Methods: Eighty-three patients who underwent mastectomy or modified radical mastectomy for histologically confirmed primary invasive carcinoma of no special type were included. Immunohistochemistry was used to assess SLC7A5/LAT1 expression. Associations with clinicopathological features and molecular groups were analyzed using the Chi-square test. Results: The mean age of SLC7A5-positive patients were 48.4 ± 10.8 years. Overall, 24.1% of patients demonstrated SLC7A5 positivity. Although SLC7A5 expression was more frequent in cases categorized as having moderate or poor prognosis based on the Nottingham Prognostic Index (NPI), this trend was not statistically significant. Similarly, no significant associations were observed between SLC7A5 expression and other clinicopathological or molecular variables. Conclusions:SLC7A5/LAT1 expression was identified in approximately one-quarter of invasive breast carcinoma cases. Its expression appeared more common in tumors with poorer NPI categories, but without statistically verified associations. These findings suggest that SLC7A5 may act independently of conventional clinicopathological parameters. Larger, longitudinal studies with survival follow-up are required to clarify its prognostic and therapeutic significance. Full article

Sarcopenia, the loss of skeletal muscle mass and function, is a common and critical comorbidity in patients with conditions frequently managed by interventional radiologists, such as liver cirrhosis and hepatocellular carcinoma (HCC). Interventional radiologists are well positioned to incorporate opportunistic screening for this condition during routine preprocedural cross-sectional imaging. This review summarizes the current evidence on how sarcopenia influences patient outcomes and informs procedural planning across a spectrum of interventional radiology (IR) procedures. In transarterial embolizations for HCC, sarcopenia is a robust independent predictor of increased mortality, with meta-analyses suggesting it may also predict a lower tumor response rate. Even earlier stages of muscle loss (pre-sarcopenia) are associated with worse survival, and dynamic changes in muscle mass post-treatment can serve as a biomarker for tumor progression. For patients undergoing transjugular intrahepatic portosystemic shunt, pre-procedural sarcopenia and myosteatosis are strong, independent predictors of both mortality and the development of post-procedural hepatic encephalopathy, with the presence of both conferring the highest risk. In the context of pre-surgical portal vein embolization, sarcopenia is consistently associated with impaired volumetric liver growth, although this does not always translate to worse short-term surgical outcomes, as functional liver regeneration may be preserved. Following percutaneous liver tumor ablation, sarcopenia is a powerful predictor of overall mortality, while its role in predicting tumor recurrence remains an area of active investigation. Finally, in non-oncologic interventions for peripheral arterial disease, sarcopenia is highly prevalent and is associated with worse functional status, higher mortality, and a significantly increased risk of major amputation after endovascular therapy. In conclusion, sarcopenia is a powerful and readily available biomarker that provides crucial prognostic information—often independent of standard clinical scores—across a wide spectrum of IR procedures. The consistent evidence supports integrating sarcopenia evaluation into routine practice to enhance risk stratification, improve patient counseling, and guide multidisciplinary treatment planning. Full article

Liposarcomas represent a heterogeneous group of malignant mesenchymal neoplasms, with diverse histological subtypes and molecular alterations. This study aimed to investigate the gene expression profiles of SOX9, GATA3, and GATA4 in liposarcoma subtypes and to assess their associations with clinicopathological parameters. Forty-two formalin-fixed, paraffin-embedded liposarcoma samples were analyzed. Total RNA was extracted, reverse-transcribed, and quantified by qRT-PCR using GAPDH as an endogenous control. Relative quantification (RQ) values were categorized, and statistical analyses included Fisher’s exact test, Kaplan–Meier survival analysis, and Cox proportional hazards modeling. SOX9 expression significantly varied among histological subtypes (p = 0.017), with ALT/WDLS cases showing a predominance of high-level expression (RQ > 50 in 12/15 cases), in contrast to myxoid subtypes clustering mainly in the 10–50 RQ range. GATA4 overexpression correlated with smaller tumor size (<100 mm) (p = 0.049), being more frequent in 15/20 small tumors compared to 10/22 larger ones. GATA3 and GATA4 demonstrated the strongest inter-gene correlation (r = 0.68, p < 0.05), suggesting possible functional interplay. Kaplan–Meier analysis revealed no statistically significant survival differences for individual gene expression, but a high combined GATA3–GATA4 signature was associated with a favorable trend. These findings indicate that SOX9, GATA3, and GATA4 are broadly upregulated in liposarcomas, with subtype- and size-dependent expression patterns. The strong association between GATA3 and GATA4 expression supports their potential synergistic role in tumor biology. Integration of these molecular markers into diagnostic and prognostic workflows may enhance subtype characterization and inform targeted therapeutic strategies. Further studies in larger cohorts are warranted to validate these biomarkers and explore their mechanistic interplay in liposarcoma pathogenesis. Full article

Non-muscle invasive bladder cancer (NMIBC) accounts for the majority of bladder cancer diagnoses and remains a clinical challenge due to its high recurrence and progression rates despite intravesical Bacillus Calmette–Guérin (BCG) therapy. In recent years, tumor-infiltrating lymphocytes (TILs) have emerged as promising biomarkers, reflecting the interplay between the tumor and host immune system. However, the evidence regarding their prognostic and predictive role is still conflicting, largely due to methodological heterogeneity, lack of standardized evaluation criteria, and limited prospective validation. This narrative review summarizes the current knowledge on TILs in NMIBC, focusing on their compartmental distribution (stromal, intraepithelial, and tumor–stroma interface), compositional diversity (CD4⁺, CD8⁺, Treg, B cells), and spatial dynamics. Special attention is given to their role in predicting response to BCG immunotherapy, the contribution of tumor-associated macrophages and tertiary lymphoid structures, and the emergence of immune escape pathways, including Programmed Death-Ligand 1 (PD-L1) and the HLA-E/NKG2A axis. Advances in digital pathology, spatial transcriptomics, and integrated immunoscore models provide more accurate metrics compared to simple cell counts, highlighting the importance of functional and spatial signatures. Despite encouraging progress, TILs are not yet ready for routine incorporation into histopathological reporting. Future directions include standardized assessment, integration with molecular biomarkers, and prospective multicenter validation to enable their translation into risk stratification and personalized therapeutic decision-making. Full article

Uterine leiomyosarcoma (uLMS) is a rare, highly aggressive malignancy of uterine smooth muscle, associated with early metastasis, frequent recurrence, and poor prognosis. Accurate preoperative diagnosis remains difficult given that clinical and radiologic features often overlap with benign leiomyomas, and no reliable biomarkers are currently available. This review summarizes recent evidence on the role of microRNAs (miRNAs) in the biology and clinical management of uLMS. Literature from molecular and translational studies was examined to identify dysregulated miRNAs, their target pathways, and potential diagnostic and therapeutic applications. uLMS displays a characteristic miRNA profile, including downregulation of tumor-suppressive miRNAs such as the miR-29 and miR-200 families and upregulation of oncogenic miRNAs including miR-21 and the miR-183~96~182 cluster, leading to activation of PI3K/AKT/mTOR signaling and epithelial–mesenchymal transition (EMT). Circulating and tissue miRNAs show promise as minimally invasive biomarkers for differentiating uLMS from leiomyomas, predicting prognosis, and guiding therapy. Emerging therapeutic approaches aim to restore the tumor-suppressive miRNAs or inhibit oncogenic ones using mimics or antagomiRs. Overall miRNAs represent critical regulators of uLMS pathogenesis and hold significant potential for precision diagnosis, prognostication, and targeted therapy, though larger validation studies and improved delivery systems are required before clinical translation. Full article

Background and Objectives: Systemic inflammation plays a critical role in cancer progression and prognosis. The Systemic Inflammation Response Index (SIRI), a novel marker integrating neutrophil, monocyte, and lymphocyte counts, has been suggested as a prognostic indicator in various malignancies. This study aimed to evaluate the prognostic significance of SIRI in patients with metastatic pancreatic cancer receiving first-line chemotherapy. Materials and Methods: This retrospective study included 147 patients with metastatic pancreatic cancer who received first-line chemotherapy or best supportive care between 2010 and 2024. Clinical and laboratory data were collected from medical records. Overall survival (OS) and progression-free survival (PFS) were assessed using the Kaplan–Meier method, and prognostic factors were identified by univariate and multivariate Cox regression analyses. Results: The median OS and PFS were 7 and 4 months, respectively. Multivariate analysis revealed that ECOG ≥ 2 (HR: 2.094, p = 0.019), liver metastasis (HR: 2.039, p = 0.027), and each unit increase in SIRI (HR: 1.156, p < 0.001) were independent predictors of poorer OS. Patients with SIRI > 1.86 had significantly shorter OS compared to those with SIRI ≤ 1.86 (median OS: 4 vs. 9 months, p = 0.019). Conclusions: SIRI is an independent prognostic marker for survival in metastatic pancreatic cancer patients undergoing first-line and subsequent lines of chemotherapy. These inflammation-based markers are simple, cost-effective tools that could be integrated into routine clinical practice to aid in risk assessment and treatment planning. Full article

Background: Patients with acute anterior circulation large-vessel occlusion (AC-LVO) stroke frequently experience poor outcomes despite successful mechanical thrombectomy (MT). Heparin-binding protein (HBP), a neutrophil-derived mediator of inflammation and vascular permeability, may contribute to neuroinflammation and prognosis; however, its role in stroke remains unclear. Methods: In this retrospective study, 163 patients with AC-LVO stroke who underwent MT were enrolled. Plasma HBP levels were measured within 24 h after thrombectomy. Functional outcomes were evaluated using the modified Rankin Scale (mRS) at 90 days, with an mRS score 3–6 suggesting a poor outcome. Multivariable logistic regression and receiver operating characteristic (ROC) analyses were performed to assess associations between HBP and outcomes. Results: Of the 163 patients, 88 (54.0%) had poor functional outcomes. The median plasma HBP level of patients with poor outcomes was significantly higher than that of patients with good outcomes (28.80 vs. 18.42 ng/mL; p < 0.001). HBP remained independently associated with poor outcome (odds ratio [OR] 1.04; 95% confidence interval [CI] 1.01–1.07; p = 0.002) after adjusting for demographic, clinical, procedural, and laboratory covariates. ROC analysis showed a modest predictive value of HBP alone (area under the curve [AUC] = 0.671), whereas adding HBP to clinical models improved prognostic accuracy (AUC = 0.835 for model 2; AUC = 0.889 for model 3). Conclusions: For patients with AC-LVO stroke, elevated plasma HBP within 24 h after MT serves as an independent predictor of unfavorable functional outcomes at 90 days. Thus, HBP may serve as a prognostic biomarker and potential target for immunomodulatory therapy. Full article

Lipocalin-2 (LCN2) is a 25 kDa glycoprotein that has been shown to be a multifunctional player in the metastasis of triple-negative breast cancer (TNBC). In physiological contexts, LCN2 exhibits bacteriostatic properties and plays key roles in iron homeostasis and the transport of hydrophobic molecules. However, several studies have shown that aberrant LCN2 expression is associated with poor prognosis in various malignancies, including breast cancer, which is the most common cancer in women worldwide and can be classified into four molecular subtypes. Among these, TNBC represents a disproportionately aggressive subtype characterized by poor prognosis and high metastatic potential. Although LCN2 has been extensively studied in breast cancer overall, its specific role in TNBC progression and metastasis is only beginning to be understood. Recent evidence suggests that LCN2 contributes to several tumor-promoting processes such as angiogenesis, therapy resistance and modulation of the tumor microenvironment. Moreover, LCN2 appears to influence organ-specific metastasis, particularly to the lung and brain, while its role in liver and bone dissemination remains unclear. Collectively, current data identify LCN2 as a critical mediator of TNBC progression and highlight its potential as a prognostic factor and modulator of disease progression. This review aims to summarize insights from both in vitro and in vivo studies, with particular focus on the role of LCN2 in the metastatic cascade, while also addressing existing research gaps and critically evaluating the current findings. Full article

Metabolic immune evasion is a major factor limiting the long-term efficacy of intravesical Bacillus Calmette–Guérin (BCG) therapy in non-muscle-invasive bladder cancer (NMIBC). TIA1 is a stress granule RNA-binding protein with liquid–liquid phase separation (LLPS) capacity. Its role in tumor metabolism and immunotherapy response has been unclear. Here, we demonstrated that high TIA1 expression was independently associated with favorable survival across multiple cohorts. Full-length TIA1 formed cytoplasmic condensates, repressed LDHA/PKM2/HK2, reduced lactate, and lowered extracellular acidification. A condensate-defective ΔLCD (deletion of the low-complexity domain) mutant was inactive. TIA1 showed physical association with these glycolytic mRNAs in human cells, consistent with mRNA-linked control. Condensate-competent TIA1 promoted CD8⁺ T-cell proliferation, increased CD69 and Granzyme-B, and reduced PD-1 in co-culture. TIMER (Tumor Immune Estimation Resource) and spatial-omics supported co-localization with tumoral CD8A. BCG induced this metabolic–immune signature in cell lines, murine models, and patient explants, but the effects were abolished by TIA1 knock-down. Conversely, TIA1 over-expression alone limited tumor growth and recapitulated BCG-mediated glycolytic restraint and T-cell activation. Together, these results support an LLPS-linked, mRNA-associated regulation of tumor glycolysis. BCG-driven glycolytic suppression and CD8⁺ T cell activation track with the condensate-forming capacity of TIA1. TIA1 emerges as a prognostic biomarker and a potential therapeutic axis to improve intravesical immunotherapy in NMIBC. Full article

Background and Objectives: The Hepatitis E Virus (HEV) is increasingly recognized as a cause of chronic infection in immunocompromised patients, but its precise role in cryptogenic cirrhosis (CC) is unclear. CC is defined as liver cirrhosis in which all known causes, including viral, autoimmune, metabolic, and alcohol-related etiologies, have been meticulously excluded. We aimed to address this gap by definitively assessing HEV’s etiological contribution in CC through seroprevalence comparison and evaluating its long-term prognostic impact on disease progression and adverse clinical outcomes. Materials and Methods: This is a retrospective, single-center, observational, and longitudinal cohort study, conducted between July 2017 and June 2025. The study included 52 CC patients, whose diagnosis was strictly confirmed by excluding all known etiologies, and 900 healthy blood donors from the same region. CC patients were retrospectively followed for five years to assess long-term clinical outcomes. We compared HEV seropositive and seronegative patients for accelerated disease progression (assessed by follow-up MELD-Na scores) and cirrhosis-related death. We employed multivariable logistic regression to adjust for demographic confounders in the prevalence comparison and multivariable COX regression for survival analysis to determine the independent prognostic role of HEV seropositivity. Results: The anti-HEV IgG seroprevalence in CC patients (42.3%) was significantly higher than in healthy donors (12.8%) (p < 0.001). Multivariable logistic regression confirmed CC status as an independent predictor of HEV seropositivity (Adjusted OR = 6.142, p < 0.001). During the five-year follow-up, the cirrhosis-related death rate was significantly higher in the anti-HEV IgG positive group (36.4% vs. 13.4%; p = 0.047), and their follow-up MELD-Na score was significantly higher (p = 0.029). However, multivariable COX analysis did not sustain anti-HEV IgG positivity as an independent risk factor for death (p = 0.294). Conclusions: HEV exposure is independently and significantly higher in CC patients. While anti-HEV IgG positivity correlates with higher mortality and accelerated disease progression in univariable analysis, its lack of independent prognostic significance suggests it may primarily function as a marker for a more advanced stage of CC or underlying immune dysfunction. Further rigorous prospective studies are necessary to precisely define HEV’s long-term prognostic role and evaluate its impact on disease progression. Full article

Background: Hepatocellular carcinoma remains a global health challenge with high mortality rates. The tumor immune microenvironment significantly impacts disease progression and survival. However, traditional analyses predominantly focus on single immune genes, overlooking the critical interplay among multiple immune gene signatures. Our study explores the prognostic significance of chemokine (C-C motif) ligand 5 (CCL5) expression and associated immune genes through an innovative combination of Autoregressive Integrated Moving Average (ARIMA) and Convolutional Neural Network (CNN) models. Methods: A time series dataset of CCL5 expression, comprising 230 liver cancer patients, was analyzed using an ARIMA model to capture its temporal dynamics. The residuals from the ARIMA model, combined with immune gene expression data, were utilized as input features for a CNN to predict survival outcomes. Survival analyses were conducted using the Cox proportional hazards model and Kaplan–Meier curves. Furthermore, the ARIMA-CNN framework’s results were systematically compared with traditional median-based stratification methods, establishing a benchmark for evaluating model efficacy and highlighting the enhanced predictive power of the proposed integrative approach. Results: CNN-extracted features demonstrated superior prognostic capability compared to traditional median-split analyses of single-gene datasets. Features derived from CD8⁺ T cells and effector T cells achieved a hazard ratio (HR) of 0.7324 (p = 0.0008) with a statistically significant log-rank p-value (0.0131), highlighting their critical role in anti-tumor immunity. Hierarchical clustering of immune genes further identified distinct survival associations. Notably, a cluster comprising B cells, Th2 cells, T cells, and NK cells demonstrated a moderate protective effect (HR: 0.8714, p = 0.1093) with a significant log-rank p-value (0.0233). Conversely, granulocytes, Tregs, macrophages, and myeloid-derived suppressor cells showed no significant survival association, emphasizing the complex regulatory landscape within the tumor immune microenvironment. Conclusions: Our study provides the first ARIMA-CNN framework for modeling gene expression and survival analysis, marking a significant innovation in integrating temporal dynamics and machine learning for biological data interpretation. This model offers deeper insights into the tumor immune microenvironment and underscores the potential for advancing precision immunotherapy strategies and identifying novel biomarkers, contributing significantly to innovative cancer management solutions. Full article