Comprehensive bioinformatics and immunohistochemical analyses identify phosphoinositide metabolism and PNPLA7 as potential biomarkers in urological cancers

Abstract

Abstract Phosphoinositides (PI) and their metabolic enzymes are known to be involved in cellular processes associated with the hallmarks of cancer. The impact of PI metabolism-related components on urinary tract (or urological) cancers, however, remains unexplored. Considering this, herein, we performed a comprehensive bioinformatic analysis on clear cell renal carcinoma, bladder cancer, and adenocarcinoma of the prostate using public databases to investigate the relative contribution of PI metabolism in these clinical phenotypes. Primarily, we computed phosphoinositide metabolism scores to assess the associated biological processes and further enriched the analysis by predicting drug sensitivity, immune profiling, and risk stratification. Besides, we utilized single-cell RNA sequencing datasets to identify intercellular communication networks associated with PI metabolism in these cancer subtypes. Of interest, our analysis identified the PNPLA7 gene as a potential biomarker in urological cancers, which we validated using immunohistochemical evaluation of clinical samples. In conclusion, our study reveals that PI metabolism is a critical prognostic biomarker for urological cancers and may guide drug therapies, including immunosuppressants. Therefore, PNPLA7 could serve as a potential target and requires further attention.