Evidence map›Paper›PMID 40916434›Full record

ArticleProtein and peptide letters2025

Mevalonate Metabolic Reprogramming Drives Cisplatin Resistance in Bladder Cancer: Mechanisms and Therapeutic Targeting.

Qixiang Fang, Chengyu You, Xi Xiao, Yang Liu, Weiguang Yang, Qingchao Li, Liangliang Qing, Zhilong Dong

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Article in Protein and peptide letters, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

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4 · The record

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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Qixiang FangDepartment of Urology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou730000, Gansu, China.
Chengyu YouDepartment of Urology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou730000, Gansu, China.
Xi XiaoDepartment of Urology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou730000, Gansu, China.
Yang LiuDepartment of Urology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou730000, Gansu, China.
Weiguang YangDepartment of Urology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou730000, Gansu, China.
Qingchao LiDepartment of Urology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou730000, Gansu, China.
Liangliang QingDepartment of Urology, Zigong Fourth People's Hospital, Zigong 643000, Sichuan, China.
Zhilong DongDepartment of Urology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou730000, Gansu, China.ORCID 0000-0002-4919-8164

Funding

Gansu Provincial Higher Education Innovation Fund 2023B-045National Natural Science Foundation of China 82160148
6 · The paper itself

Abstract

introductionDysregulation 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.

methodsTranscriptomic 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.

resultsNMF 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.

conclusionMevalonate 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.

Indexed as

Antineoplastic AgentsCisplatinDrug Resistance, NeoplasmMevalonic AcidUrinary Bladder NeoplasmsCell Line, TumorFemaleGene Expression Regulation, NeoplasticHumansMaleMetabolic ReprogrammingPrognosisAntineoplastic AgentsCisplatinMevalonic AcidBladder cancergene signature.immune microenvironmentmevalonate metabolismplatinum resistanceprognosis

Identifiers

PMID40916434

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