Abstract 327P
Background
Bladder cancer (BCa) remains a clinical challenge due to high mortality rates and limited diagnostic methods. Early detection and accurate response prediction are essential for improving prognosis and treatment strategies. High-throughput sequencing shows promise in enhancing BCa diagnostics. Immune checkpoint therapies (ICTs) have significantly improved BCa outcomes but are often limited by tumor heterogeneity and complex multi-omics changes.
Methods
We identified methylation-regulated differentially expressed genes (DEGs) in BCa through high-throughput sequencing. Survival analysis determined the prognostic significance of ADCYAP1. Differential expression and methylation levels of ADCY2 and ADCYAP1 were analyzed in 12,452 pan-cancer samples from RENJI cohort. The sensitivity of BCa to chemotherapeutic agents was predicted based on methylation levels. We evaluated the correlation between ADCYAP1 expression and immune cell infiltration in 408 BCa patients from Renji Hospital, stratifying them into ADCYAP1ˆhigh and ADCYAP1ˆlow groups.
Results
ADCYAP1 methylation showed a strong inverse correlation with its mRNA expression (Correlation = -0.26, FDR = 9.2e-08). Elevated ADCYAP1 expression predicted poorer survival outcomes for BCa patients. The sensitivity of BCa to docetaxel was consistent with ADCYAP1 mRNA expression. Overexpression of ADCYAP1 reduced ATP synthase activity in BCa cells under varying docetaxel concentrations. High ADCYAP1 expression was associated with decreased T cells, endothelial cells, NK cells, and mast cells, but increased macrophage infiltration, particularly M2 macrophages. Lower ADCYAP1 methylation levels predicted poorer overall survival in BCa patients receiving ICTs.
Conclusions
ADCYAP1 gene methylation is a valuable biomarker for predicting the immune microenvironment and prognosis of BCa. The Renji Hospital cohort study validates the clinical significance of ADCYAP1 methylation, highlighting its potential utility in personalized medicine for BCa patients.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The author.
Funding
Has not received any funding.
Disclosure
The author has declared no conflicts of interest.