ArticleDiscover oncology2025
A GRK5 centered prognostic framework for bladder cancer based on palmitoylation and epigenetic regulation.
Article in Discover oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundBladder cancer (BLCA) is a common malignancy with high recurrence and poor prognosis. Palmitoylation, a reversible lipid modification, plays a critical role in cancer progression. However, its prognostic value in BLCA remains unclear.
methodsWe analyzed 3629 palmitoylation-related genes (PRGs) from the TCGA-BLCA and GEO datasets. Differentially expressed PRGs were identified, and a prognostic signature was constructed through Cox and LASSO regression analyses. Survival analysis, ROC curves, immune microenvironment profiling, drug sensitivity prediction, and mutational landscape comparison were performed. Mendelian randomization (MR) and mediation analyses explored the causal role of DNA methylation and gene expression, focusing on GRK5.
resultsA 13-PRG prognostic model was established and validated internally and externally, with AUCs exceeding 0.7. High-risk patients exhibited poorer survival, a distinct immune landscape, and altered drug sensitivities. Mutation analysis showed higher RB1 mutation rates in the high-risk group. MR and mediation analyses identified GRK5 as a key gene linking DNA methylation to BLCA risk, with cg09337049 methylation significantly suppressing GRK5 expression and influencing disease development.
conclusionThis study presents the first palmitoylation-related prognostic model for BLCA, highlighting GRK5 methylation as a potential biomarker for early detection and personalized treatment.
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