Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Introduction: Dysregulation of mevalonate metabolism is a hallmark of tumorigenesis and therapy resistance across malignancies, though its role in bladder cancer remains unclear. This study aimed to elucidate its impact on prognosis and cisplatin chemosensitivity in bladder cancer.
Methods: Transcriptomic data and clinical information of bladder cancer patients were obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. Non-negative matrix factorization (NMF) was used to cluster mevalonate metabolism-related genes into distinct metabolic subtypes (C1 and C2). Associations between mevalonate metabolism, clinical characteristics, immune infiltration, and cisplatin resistance were analyzed using Gene Set Variation Analysis (GSVA), Kaplan-Meier survival analysis, single-sample Gene Set Enrichment Analysis (ssGSEA), and in vitro experiments.
Results: NMF clustering classified bladder cancer patients into two metabolic subtypes (C1/C2). The C1, characterized by higher mevalonate metabolism (MVAscore), was associated with a poorer prognosis, shorter overall survival (OS), and higher T-stage and pathological grades. Immune analysis showed lower immune cell infiltration in C1. Immune infiltration analysis revealed significantly lower immune infiltration levels in the C1. Further analysis revealed a positive correlation between mevalonate metabolism and platinum resistance, with a notable increase in mevalonate metabolism observed in cisplatin-resistant bladder cancer cells. In vitro, simvastatin inhibited the proliferation of bladder cancer cells and enhanced their sensitivity to cisplatin.
Discussion: Mevalonate metabolism drives BCa heterogeneity and chemoresistance while suppressing anti-tumor immunity. Its dysregulation serves as both a prognostic biomarker and a target for therapeutic intervention.
Conclusion: Mevalonate metabolism contributes to cisplatin resistance in bladder cancer and represents a potential therapeutic target. Simvastatin targeting this pathway enhances the efficacy of cisplatin, providing a novel personalized chemotherapy strategy.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.2174/0109298665403178250806111943 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Long-term complications in patients with bladder-prostate rhabdomyosarcoma treated with brachytherapy: a systematic review.
Pediatr Surg Int
September 2025
Pediatric Surgery Unit, Department of Women's and Children's Health, University of Padua, Via Nicolò Giustiniani, 35100, Padua, Italy.
Introduction: Brachytherapy has been used for the multimodal treatment of pediatric bladder-prostate rhabdomyosarcoma in the last two decades. The aim of this systematic review is to gather the current evidence about this innovative technique with a special focus on long-term outcomes.
Methods: According to PRISMA criteria, PubMed, Scopus, and Web of Science were searched for papers published between 2000 and 2022.
Dosimetry evaluation and uncertainty analysis of Cobalt-60 HDR brachytherapy for cervical cancer in resource-limited settings.
J Cancer Res Clin Oncol
September 2025
Cancer Treatment and Nuclear Cardiology Department, Al Azhar University, Cairo, Egypt.
Background: High-dose-rate (HDR) brachytherapy is essential in the treatment of locally advanced cervical cancer. While Iridium-192 (Ir-192) is commonly used, its short half-life imposes logistical and financial constraints, particularly in low- and middle-income countries (LMICs). Cobalt-60 (Co-60), with a longer half-life and lower operational costs, is a viable alternative.
View Article and Find Full Text PDFLoss of METTL3 m6A methyltransferase results in short-term progression and poor treatment outcome of bladder cancer patients.
Int J Cancer
September 2025
Department of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, Athens, Greece.
Bladder cancer (BlCa) exhibits a highly heterogeneous molecular landscape and treatment response, underlining the pressing need for personalized prognosis. N6-methyladenosine (m6A) constitutes the most abundant RNA modification, modulates RNA biology/metabolism, and maintains cellular homeostasis, with its dysregulation involved in cancer initiation and progression. Herein, we evaluated the clinical value of METTL3 m6A methyltransferase, the main catalytic component of m6A methylation machinery, in improving BlCa patients' risk stratification and prognosis.
View Article and Find Full Text PDFOncolytic virus therapy for nonmuscle-invasive bladder cancer: current status and future directions.
Curr Opin Urol
September 2025
Department of Urology, Faculty of Medicine, University of Toyama, Toyama, Japan.
Purpose Of Review: Nonmuscle-invasive bladder cancer (NMIBC) patients with BCG-unresponsive disease have limited treatment options beyond radical cystectomy. With ongoing BCG shortages and the urgent need for bladder-preserving alternatives, this review examines the emerging role of oncolytic virus therapy as a novel intravesical treatment approach for this challenging patient population.
Recent Findings: Multiple oncolytic viral platforms have entered clinical trials for NMIBC treatment, demonstrating promising efficacy and safety profiles.