Search Results (112)

Objectives: To assess amide proton transfer weighted (APTw) MR imaging capabilities in differentiating high-grade glial tumors across alpha-thalassemia/mental retardation X-linked (ATRX) expression, tumor-suppressor protein p53 expression (p53), O6-methylguanine-DNA methyltransferase promoter (MGMTp) methylation, isocitrate dehydrogenase (IDH) status, and proliferation marker Ki-67 (Ki-67 index) as a preoperative diagnostic aid. Material & Methods: A total of 42 high-grade glioma WHO grade 4 (HGG) patients were evaluated prospectively (30 males and 12 females). All patients were examined using conventional MRI, including the following: T1w-MPRAGE pre- and post-contrast administration, conventional T2w and 3D FLAIR, and APTw imaging with a 3T MR scanner. Receiver operating characteristic (ROC) curves were calculated for the APTw% mean, median, and max signal for the different molecular biomarkers. A logistic regression model was constructed for combined mean and median APTw% signals for p53 expression. Results: The whole-tumor max APTw% signal could significantly differentiate MGMTp from non-MGMTp HGG, p = 0.035. A cutoff of 4.28% max APTw% signal yielded AUC (area under the curve) = 0.702, with 70.6% sensitivity and 66.7% specificity. The mean/median APTw% signals differed significantly in p53 normal versus p53-overexpressed HGG s: 1.81%/1.83% vs. 1.15%/1.18%, p = 0.002/0.006, respectively. Cutoffs of 1.25%/1.33% for the mean/median APTw% signals yielded AUCs of 0.786/0.757, sensitivities of 76.9%/76.9%, and specificities of 50%/66.2%, p = 0.002/0.006, respectively. A logistic regression model with a combined mean and median APTw% signal for p53 status yielded an AUC = 0.788 and 76.9% sensitivity and 66.2% specificity. ATRX-, IDH- wild type (wt) vs. mutation (mut), and the level of Ki-67 did not differ significantly, but trends were found: IDH-wt and low Ki-67 showed higher mean/median/max APTw% signals vs. IDH-mut and high Ki-67, respectively. ATRX-wt vs. mutation showed higher mean and median APTw% signals but lower max APTw% signal. Conclusions: APTw imaging can potentially be a useful marker for the stratification of p53 expression and MGMT status in high-grade glioma in the preoperative setting and potentially aid surgical decision-making. Full article

Background: Glioblastoma (GBM) remains almost uniformly fatal, owing in part to therapy-resistant cancer stem-like cells (CSCs) and to temozolomide (TMZ) resistance driven by O⁶-methylguanine-DNA methyltransferase (MGMT). Differentiation therapy with all-trans retinoic acid (ATRA) has the potential to attenuate stemness and sensitize GBM to TMZ. We therefore asked whether ATRA reduces expression of key CSC markers and MGMT in established GBM lines. Methods: Two established human GBM cell lines, U87-MG and A172, were cultured under neurosphere-promoting conditions to enrich for potential stem-like subpopulations. Cells were treated with either 1 µM ATRA or vehicle control (DMSO) for 5 days. Total RNA was extracted, and cDNA was synthesized. Quantitative Real-Time PCR (qPCR) assessed relative mRNA expression levels of key stemness transcription factors (SOX2, NES) and the DNA repair gene MGMT and corresponding protein levels were measured by an Enzyme-Linked Immunosorbent Assay (ELISA). Gene expression was normalized to the geometric mean of two validated housekeeping genes (GAPDH, ACTB). Relative quantification was calculated using the ΔΔCt method, and statistical significance was determined using Student’s t-tests. Results: ATRA markedly suppressed stemness and MGMT in both lines. In U87-MG, SOX2 mRNA fell 3.7-fold (p = 0.0008) and protein 2.99-fold (148.3 ± 6.0 → 49.7 ± 2.7 pg µg⁻¹; p = 0.0002); Nestin dropped 4.1-fold (p = 0.0005) and 3.51-fold (450.0 ± 17.3 → 128.3 ± 4.4 pg µg⁻¹; p = 0.00008). MGMT decreased 2.6-fold at transcript level (p = 0.0065) and 2.11-fold at protein level (81.7 ± 4.4 → 38.7 ± 1.8 pg µg⁻¹; p = 0.0005). In A172, SOX2 was reduced 2.9-fold (p = 0.0041) and 2.31-fold (p = 0.0007); Nestin 3.3-fold (p = 0.0028) and 2.79-fold (p = 0.00009). MGMT declined 2.2-fold (p = 0.0132) and 1.82-fold (p = 0.0015), respectively. Conclusions: Five-day exposure to ATRA diminishes SOX2, Nestin, and MGMT at both mRNA and protein levels in stem-enriched GBM cultures, supporting the premise that ATRA-induced differentiation can concurrently blunt CSC traits and TMZ-resistance mechanisms. These data provide a molecular rationale for testing ATRA in combination regimens aimed at improving GBM therapy. Full article

Temozolomide (TMZ) remains the frontline chemotherapy for gliomas; yet its clinical efficacy is significantly compromised by inherent instability and the emergence of resistance mechanisms. To surmount these challenges, we engineered a squalenoylated TMZ nanoparticle (SQ-TMZ NPs) via conjugation of TMZ with squalene, enabling enhanced drug stability and improved therapeutic potency against glioblastoma cells. The resulting SQ-TMZ NPs exhibited a precisely controlled nanoscale architecture (~126 nm), demonstrating exceptional stability under physiological and storage conditions, with minimal hemolytic toxicity (<5%). Notably, these nanoparticles conferred superior cytotoxicity in TMZ-resistant glioblastoma T98G cells, attributed to the amplification of intracellular reactive oxygen species (ROS) and DNA damage, along with MGMT (O-6-methylguanine-DNA methyltransferase) expression suppression. Furthermore, in vivo imaging confirmed their efficient blood–brain barrier (BBB) penetration and selective tumor accumulation. This study presents a transformative approach by integrating prodrug self-assembly with targeted drug delivery to not only enhance TMZ stability but also decisively reverse glioblastoma resistance, offering a compelling therapeutic advancement. Full article

Background: Glioma is the most common type of malignant brain tumor. Temozolomide (TMZ) is a limited systematic treatment option for glioma, including low-grade glioma (LGG) and glioblastoma (GBM). However, not all patients benefit from TMZ and some develop resistance to it. MGMT methylation has been used to identify patients who may benefit from TMZ, but it is not effective in all cases. Objectives: There is an urgent need for new biomarkers to predict the survival of patients who receive TMZ. Methods: We utilized a recently developed method called REdiscoverTE to precisely measure the expression of transposable elements (TE). We performed Cox regression analysis to assess the predictive ability for prognosis and conducted a series of correlation studies to uncover potential mechanisms. Results: We identified three TEs, LTR81B, LTR27B, and MER39B, that were strongly predictive of longer survival in glioma patients receiving chemotherapy. We discovered that the expression of these TEs was positively associated with immune cells that enhance the immune system and negatively associated with immune cells suppressing the immune response, as well as molecules that control immune checkpoints. These three TEs were also found to predict better survival in patients receiving immunotherapy. Conclusions: In conclusion, we demonstrate that the expression of TEs can serve as a novel biomarker for the overall survival of glioma patients who receive TMZ chemotherapy or immunotherapy. Full article

Background and Objectives: Glioblastoma (GBM) is among the most aggressive and lethal primary brain tumors, characterized by high heterogeneity, invasive growth, and resistance to conventional therapies. The 2021 WHO classification highlights the importance of molecular diagnostics, integrating genetic, transcriptomic, and epigenetic alterations alongside histological and immunohistochemical criteria. Materials and methods: Key molecular regulators, including ATRX, OLIG2, MGMT, and IDH2, play critical roles in chromatin remodeling, transcriptional reprogramming, DNA repair, and metabolic adaptation. However, their specific expression patterns and functional roles in GBM remain incompletely understood. This study utilizes publicly available data from The Cancer Genome Atlas (TCGA) to assess the transcriptional profiles of ATRX, OLIG2, MGMT, and IDH2 in GBM, aiming to identify potential biomarkers and therapeutic targets. Results: The expression analysis revealed that ATRX is downregulated at the gene level but overexpressed at the protein level, while OLIG2 is consistently overexpressed at both levels. MGMT showed no statistically significant changes in either gene or protein expression, whereas IDH2 was not significantly altered at the gene level but was downregulated at the protein level (p < 0.05). These discrepancies suggest potential post-transcriptional regulatory mechanisms influencing GBM molecular profiles. Notably, OLIG2 and MGMT expression correlated significantly with patient survival (p < 0.05), whereas ATRX and IDH2 did not reach statistical significance. Conclusions: Understanding these molecular relationships provides valuable insights into potential therapeutic strategies, paving the way for precision oncology approaches and combination therapies targeting multiple pathways simultaneously. Full article

The methylation status of the MGMT gene promoter is recognized as a key predictive biomarker for glioblastoma patients, influencing treatment decisions and outcomes. Emerging evidence suggests that enhancer methylation may also play a role in gene regulation and is associated with various clinical parameters, genetic variants, and demographic factors. This study aimed to assess DNA methylation levels in intergenic and intragenic MGMT enhancers to investigate their relationship with MGMT promoter methylation, MGMT protein expression, and clinical and demographic characteristics in glioblastoma. We developed 18 pyrosequencing assays to analyze 54 CpGs, including 34 in intergenic and 20 in intragenic enhancers. The assays were applied to tumor cells derived from 38 glioma patients. Intragenic enhancer CpGs showed significantly higher methylation than intergenic enhancer CpGs. Intragenic enhancer methylation showed a strong negative correlation with MGMT promoter methylation. For several CpGs in intragenic enhancers, an inverse L-shaped relationship between methylation levels and MGMT expression was observed. We identified distinct associations between enhancer methylation and clinical and demographic parameters. Intergenic enhancer methylation was primarily linked to the TERT SNP rs2853669 genotype, Ki-67 expression, age, and sex, whereas intragenic enhancer methylation was associated with MGMT promoter methylation, MGMT expression, overall survival, and progression-free survival. Further studies with larger patient cohorts are needed to validate the clinical relevance of intergenic and intragenic MGMT enhancer methylation in glioblastoma. Full article

(1) Background: Glioblastoma (GBM) is the most aggressive and common primary malignant brain tumor in adults, constituting 45.6% of tumors. We explored the impact of gene methylation of the O-6-Methylguanine-DNA Methyltransferase (MGMT) and the Transforming Growth Factor Beta (TGFB) gene complex using the TCGA dataset for GBM patients. (2) Methods: We implemented a multivariate Cox proportional hazards model to directly compare hazard ratios for TGFB1/2/3 and MGMT methylation in relation to OS, considering male versus female, age at diagnosis, and age interactions with TGFB2 gene methylation and sex variables. Reactome analysis was performed to identify enriched pathways negatively correlated with TGFB2 methylation. (3) Results: The GBM patients had high levels of TGFB2 gene methylation; this primarily benefited the young adult male patients, and multivariate analysis exhibited a significantly improved OS prognosis HR (95% CI range) = 0.04 (0.006–0.274); p = 0.001) relative to the TGFB1^highMe (HR (95% CI range) = 0.657 (0.454–0.951); p = 0.026) and MGMT^highMe (HR (95% CI range) = 0.667 (0.475–0.936); p = 0.019) groups of GBM patients. The Reactome pathways collectively represented T-cell activation, differentiation, effector functions, antigen presentation, and Toll-like receptor pathways. Gene level mRNA expression highlighted four positive prognostic genes upregulated in tumor tissues, and their expression was validated in independent single-cell RNA-seq experiments. These genes were highly expressed in macrophages (HIF1A, TRIM22, IRAK4, PARP9). In contrast, MALT1 mRNA expression was the only gene product with a negative prognostic impact on OS in GBM patients (HR (95% CI range) = 1.997 (1.1–3.625); p = 0.023). (4) Conclusions: Increased levels of TGFB2 gene methylation predict improved OS, especially in young adult male GBM patients, above that of MGMT gene methylation, and should be considered during the administration of mRNA-based TGFB2 therapies. Full article

Circulating small extracellular vesicles (sEVs) are emerging as potential biomarkers for glioblastoma progression. This study aimed to compare the levels of matrix metalloproteinases (MMP2 and MMP9), terminal complement complex (C5b-9), and VEGF-A in circulating sEVs in glioblastoma patients (GBMPs) with and without tumor recurrence. Using differential ultracentrifugation, sEVs were isolated from blood samples of GBMPs with no tumor recurrence for over one year (n = 6) and after first relapse (n = 14). The vesicles were characterized and quantified using flow cytometry. In both groups, C5b-9 was predominantly detected on tumor-specific circulating sEVs (glial fibrillary acidic protein (GFAP)-positive sEVs) with high VEGF-A expression, while C5b-9 was significantly less frequent on sEVs with low VEGF-A expression (p < 0.05). GFAP+VEGF+dimMMP2-C5b-9+ vesicles were rarely detected in GBMPs without relapse, suggesting their potential utility as biomarkers for a favorable relapse-free prognosis. In recurrent GBMPs, a positive correlation was observed between GFAP+VEGF+bright MMP2+C5b-9+ sEVs and MGMT gene promoter methylation levels (r = 0.543, p < 0.05). Additionally, a trend toward a negative correlation was found between GFAP+VEGF+bright MMP2+C5b-9- sEVs and mutant p53 expression in primary tumor tissue (r = −0.44, p = 0.114). These findings suggest that sEV profiles may serve as valuable prognostic markers for glioblastoma recurrence and treatment responses. Full article

Glioblastoma (GB) is a highly malignant brain tumor with a poor prognosis, with a median survival of only 14.6 months despite aggressive treatments. Resistance to chemotherapy, particularly temozolomide (TMZ), is a significant challenge. The DNA repair enzyme MGMT and glioblastoma stem cells (GSCs) often mediate this resistance. Recent studies highlight the therapeutic potential of natural compounds, particularly delphinidins, found in deep purple berries. Delphinidins are known for their ability to inhibit NF-κB signaling, a critical pathway for GB progression, chemoresistance, and MGMT expression. Our research demonstrates that glycosylated delphinidins have potential adjuvant use in the treatment of GB, offering a promising natural strategy to combat TMZ resistance. Specifically, we observed that delphinidin 3,5 di-glucoside has potent anticancer effects when used alone. Meanwhile, delphinidin 3 glucoside acted in synergy with temozolomide to decrease cell viability, highlighting its potential as an adjuvant. It also exerted a faster and more sustained inhibition of NF-κB, highlighting its potential for long-lasting therapeutic effects. These findings open new avenues for targeted therapies against glioblastoma, particularly to overcome treatment resistance. Full article

Background/Objectives: Glioblastoma (GBM) is the most common malignant primary central nervous system tumor with extremely poor prognosis and survival outcomes. Non-invasive methods like radiomic feature extraction, which assess sub-visual imaging features, provide a potentially powerful tool for distinguishing molecular profiles across groups of patients with GBM. Using consensus clustering of MRI-based radiomic features, this study aims to investigate differential gene expression profiles based on radiomic clusters. Methods: Patients from the TCGA and CPTAC datasets (n = 114) were included in this study. Radiomic features including T1, T1 with contrast, T2, and FLAIR MRI sequences were extracted using PyRadiomics. Selected radiomic features were then clustered using ConsensusClusterPlus (k-means base algorithm and Euclidean distance), which iteratively subsamples and clusters 80% of the data to identify stable clusters by calculating the frequency in which each patient is a member of a cluster across iterations. Gene expression data (available for n = 69 patients) was analyzed using differential gene expression (DEG) and gene set enrichment (GSEA) approaches, after batch correction using ComBat-seq. Results: Three distinct clusters were identified based on the relative consensus matrix and cumulative distribution plots (Cluster 1, n = 25; Cluster 2, n = 46; Cluster 3, n = 43). No significant differences in patient demographic characteristics, MGMT methylation status, tumor location, or overall survival were identified across clusters. Differentially expressed genes were identified in Cluster 1, which have been previously associated with GBM prognosis, recurrence, and treatment sensitivity. GSEA of Cluster 1 showed an enrichment of genes upregulated for immune-related and DNA metabolism pathways and genes downregulated in pathways associated with protein and histone deacetylation. Clusters 2 and 3 exhibited fewer DEGs which failed to reach significance after multiple testing corrections. Conclusions: Consensus clustering of radiomic features revealed unique gene expression profiles in the GBM cohort which likely represent subtle differences in tumor biology and radiosensitivity that are not visually discernible, underscoring the potential of radiomics to serve as a non-invasive alternative for identifying GBM molecular heterogeneity. Further investigation is still required to validate these findings and their clinical implications. Full article

Background: Molecular profiles can predict which patients will respond to current standard treatment and new targeted therapy regimens. Using data from a highly diverse population of approximately three million in Southeast London and Kent, this study aims to evaluate the prevalence of IDH1 mutation and MGMT promoter methylation in the gliomas diagnosed in adult patients and to explore correlations with patients’ demographic and clinicopathological characteristics. Methods: Anonymised data on 749 adult patients diagnosed with a glioma in 2015–2019 at King’s College Hospital were extracted. Univariable and multivariable logistic regressions were used to estimate odds ratios (ORs) for expressing IDH1 mutation and MGMT promoter methylation, based on each patient’s age, sex, ethnicity, histology, tumour location and extent of resection. The Kaplan–Meier method was used to estimate the overall survival functions. Results: A total of 19.5% of cases were IDH1-mutated. Being 39 years and younger (OR 5.48, 95% CI 3.17–9.47), from Asian/Asian British background (OR 3.68, 95% CI 1.05–12.97), having MGMT methylation (OR 15.92, 95% CI 7.30–34.75), an oligodendroglioma diagnosis (OR 7.45, 95% CI 2.90–19.13) and receiving a gross total/total microscopic resection (OR 1.95, 95% CI 1.24–3.08) were each univariately correlated with IDH1 mutation. MGMT methylation association persisted on adjustment (OR 14.13, 95% CI 3.88–51.43). MGMT promoter methylation was seen in 54.3% of gliomas. In the univariate adjusted ORs, being younger than 39 years (OR 2.56, 95% CI 1.48–4.43), female (OR 1.52, 95% CI 1.11–2.08), having IDH1 mutation (OR 15.92, 95% CI 7.30–34.75) and an oligodendroglioma diagnosis (OR 6.20, 95% CI 1.33–28.88) were associated with MGMT methylation. Being female (OR 1.75, 95% CI 1.22–2.51) and having an IDH1 mutation (OR 15.54, 95% CI 4.73–51.05) persisted after adjustment for age, sex, ethnicity, histology, tumour location and extent of resection. IDH1 mutant and MGMT methylated gliomas were associated with frontal lobe location. Survival analysis showed that patients with both IDH1 mutation and MGMT methylation had significantly better survival than those with either molecular marker alone. Over a 3-year period, women with unmethylated MGMT promoters generally had better survival than men with unmethylated MGMT. Conclusion: This study showed that the molecular markers of IDH1 mutation and MGMT promoter methylation were associated with age, sex, Asian/Asian British ethnic group, tumour histology, anatomical location and extent of resection. This study has demonstrated the importance of assessing glioma molecular markers in the clinical setting and the need to stratify patients according to their clinicopathological characteristics. Full article

Background: Glioblastoma IDH-wildtype (GBM IDH-wt) is the most aggressive brain tumor in adults and is characterized by an immunosuppressive microenvironment. Different factors shaping its tumor microenvironment (TME) regulate tumor progression and treatment response. The aim of this study was to characterize the main immunosuppressive elements of the GBM IDH-wt TME. Methods: Immunohistochemistry for CD3, CD4, CD8, CD163, programmed death ligand 1 (PD-L1) and programmed death 1 (PD1) was performed on surgical tumor specimens from patients diagnosed with GBM IDH-wt, according to the CNS WHO 2021 criteria. The impact of categorical variables on time-dependent outcomes such as overall survival (OS) and progression-free survival (PFS) has been estimated through the Kaplan–Meier method. Results: We included 30 patients (19 males and 11 females), median age of 59.8 years (range 40.2–69.1 years). All patients underwent surgery followed by temozolomide concurrent with and adjuvant to radiotherapy. MGMT was methylated in 14 patients (47%) and unmethylated in 16 patients (53%). The overall absolute percentages of CD4+ lymphocytes, both intratumoral and perivascular, were significantly more represented than CD8+ lymphocytes in the TME (p = 0.02). A low density of CD4+ lymphocytes (≤10%) was found to be a favorable prognostic factor for GBM outcome (p = 0.02). Patients with MGMT methylated and unmethylated tumors exhibited a distinct TME composition, with a significant higher number of perivascular CD8+ lymphocytes (p = 0.002), intratumoral CD8+ lymphocytes (p = 0.0024) and perivascular CD4+ lymphocytes (p = 0.014) in MGMT unmethylated tumors. PD-L1 expression in tumor cell surface was observed in four tumors (13.3%), and PD1 expression in infiltrating T lymphocytes was observed in nine (30%) tumors, with predominantly perivascular distribution. Conclusions: MGMT methylated and unmethylated tumors exhibit different immune profiles, likely reflecting the different biology of these tumors. The expression of PD-L1 in GBM IDH-wt patients is confined to a small subpopulation. While we found a significant association between low CD4+ lymphocyte density (≤10%) and survival, given the small numbers of our cohort, the prognostic value of CD4+ lymphocyte density will need to be validated in large-scale studies. Full article

Laryngeal cancer poses a substantial challenge in head and neck oncology, and there is a growing focus on customized medicine techniques. The present state of gene expression indicators in laryngeal cancer and their potential to inform tailored therapy choices are thoroughly examined in this review. We examine significant molecular changes, such as TP53, CDKN2A, PIK3CA, and NOTCH1 mutations, which have been identified as important participants in the development of laryngeal cancer. The study investigates the predictive and prognostic significance of these genetic markers in addition to the function of epigenetic changes such as the methylation of the MGMT promoter. We also go over the importance of cancer stem cell-related gene expression patterns, specifically CD44 and ALDH1A1 expression, in therapy resistance and disease progression. The review focuses on indicators, including PD-L1, CTLA-4, and tumor mutational burden (TMB) in predicting immunotherapy responses, highlighting recent developments in our understanding of the intricate interactions between tumor genetics and the immune milieu. We also investigate the potential for improving prognosis accuracy and treatment selection by the integration of multi-gene expression panels with clinicopathological variables. The necessity for uniform testing and interpretation techniques is one of the difficulties, in implementing these molecular insights into clinical practice, that are discussed. This review seeks to provide a comprehensive framework for promoting personalized cancer therapy by combining the most recent data on gene expression profiling in laryngeal cancer. Molecularly guided treatment options may enhance patient outcomes. Full article

Objective: Epigenetic tumor characteristics are in focus for glioblastoma prognosis. This raises the question if these characteristics present with stable expression during the progression of the disease, and if potential temporal instability might influence their prognostic value. Methods: A total of 44 patients suffering from glioblastoma who were treated for their primary and relapse tumors were included in the study. Tumor specimens from the initial and recurrent tumor resection were subjected to evaluation of MGMT, p15, and p16 methylation statuses. MiRNA-21, -24, -26a, and -181d expression was evaluated as well. The stability of these epigenetic markers during the progression of the disease was correlated with further clinical data. A Cancer Genome Atlas (TCGA) dataset of 224 glioblastoma patients was used as an independent cohort to validate the results. Results: Instability was observed in all examined epigenetic markers. MGMT methylation changed in 30% of patients, p15 methylation changed in 35%, and p16 methylation changed in 37.5% of cases. MiRNA expression in corresponding initial and relapse tumor specimens varied considerably in general, individual cases presented with a stable expression. Patients with a decreased expression of miRNA-21 in their recurrence tumor showed significantly longer overall survival. These results are supported by the data from TCGA indicating similar results. Conclusions: Epigenetic characteristics may change during the course of glioblastoma disease. This may influence the prognostic value of derived molecular markers. Full article

Overcoming temozolomide (TMZ)-resistance is a major challenge in glioblastoma therapy. Therefore, identifying the key molecular player in chemo-resistance becomes urgent. We previously reported the downregulation of PDCD10 in primary glioblastoma patients and its tumor suppressor-like function in glioblastoma cells. Here, we demonstrate that the loss of PDCD10 causes a significant TMZ-resistance during treatment and promotes a rapid regrowth of tumor cells after treatment. PDCD10 knockdown upregulated MGMT, a key enzyme mediating chemo-resistance in glioblastoma, accompanied by increased expression of DNA mismatch repair genes, and enabled tumor cells to evade TMZ-induced cell-cycle arrest. These findings were confirmed in independent models of PDCD10 overexpressing cells. Furthermore, PDCD10 downregulation led to the dedifferentiation of glioblastoma cells, as evidenced by increased clonogenic growth, the upregulation of glioblastoma stem cell (GSC) markers, and enhanced neurosphere formation capacity. GSCs derived from PDCD10 knockdown cells displayed stronger TMZ-resistance and regrowth potency, compared to their parental counterparts, indicating that PDCD10-induced stemness may independently contribute to tumor malignancy. These data provide evidence for a dual role of PDCD10 in tumor suppression by controlling both chemo-resistance and dedifferentiation, and highlight PDCD10 as a potential prognostic marker and target for combination therapy with TMZ in glioblastoma. Full article