Establishment of a m6 A-associated lncRNAs-derived risk model for enhanced patient prognosis stratification and personalized therapy approaches in bladder cancer.

introductionBladder cancer (BCa) is a leading malignancy in the urinary tract system, often resulting in poor prognosis due to rapid relapse and metastasis, with a low 5-year survival rate. Although the role of N6-methyladenosine (m6A) methylation and long noncoding RNAs (lncRNAs) is implicated in BCa progression, research on how lncRNAs influence BCa prognosis and potential therapeutic interventions remains scarce.

methodsRNA expression profiles and gene mutations for 406 BCa patients were retrieved from the The Cancer Genome Atlas (TCGA) database. A comprehensive dataset was established to correlate lncRNAs with 21 identified m6A-associated genes, categorized into writers, erasers, and readers. Pearson correlation analysis between these m6A genes and lncRNAs was performed and a prognostic model derived from m6A-associated lncRNAs was developed. Immune infiltration was analyzed using multiple evaluative methods and the correlation between single nucleotide variant (SNV) mutations and drug sensitivity was assessed for the correlative relationship with the m6A-associated lncRNA-derived risk scores.

resultsWe identified 3,462 m6A-associated lncRNAslinked to BCa prognosis, of which 238 lncRNAs showed significant associations with overall survival in BCa patients. A m6A-associated lncRNA-derived risk model comprising 26 selected lncRNAs was developed using Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression, where BCa patients with higher m6A-associated lncRNA-derived risk scores had poorer outcomes. The prognostic significance and reliability was validated, with an area under the curve (AUC) value exceeding 0.7 at multiple time points. Additionally, a nomogram integrating clinical features and m6A-associated lncRNA-derived risk scores had enhanced prognostic accuracy over other clinical indicators, with promise for clinical decision-making. A negative correlation was observed between m6A-associated lncRNA-derived risk scores and tumor mutational burden (TMB). Moreover, patients with high m6A-associated lncRNA-derived risk score group showed significant enrichment of regulatory T cells (Tregs), M2 macrophages, and fibroblasts, highlighting the potential involvement of immune and stromal cells in these BCa patients.

conclusionThese findings highlight the prognostic value and clinical relevance of m6A-associated lncRNAs in BCa for future patient stratification and personalized therapy approaches.