Multi-Omics Analysis of the Dual Role of PIP5K1B in Gastric Adenocarcinoma:Regulation of Myofibroblasts, Remodeling of the ImmuneMicroenvironment, and Novel Strategies for Precision Treatment

OBJECTIVE: Phosphatidylinositol-4-phosphate 5-kinase type 1 beta (PIP5K1B), an enzyme linked to actin cytoskeleton dynamics, has a paradoxical role in cancer. While pan-cancer analyses show its dual nature, its impact on overall survival (OS) in stomach adenocarcinoma (STAD) is unclear. METHODS: We combined bulk RNA sequencing data (TCGA/GTEx, 33 cancers) and single- cell transcriptomics data (STAD cohort) to track PIP5K1B expression in STAD. Cox regression and Kaplan-Meier models assessed their prognostic effect on OS, with immune infiltration and methylation-epigenetic correlation analyses. GDSC pharmacogenomic data evaluated drug sensitivity links. RESULTS: Pan-cancer analysis found PIP5K1B had a unique prognostic impact in STAD, with high expression raising death risk (OS: hazard ratios (HR) = 1.55, 95% confidence interval [CI] = 1.31 - 1.84, P = 3.5e-07). Single-cell mapping showed PIP5K1B in tumor-associated myofibroblasts, regulating tumor cell antigen processing via toll-like receptor signaling. Clinically, STAD patients had higher PIP5K1B expression (P = 0.0013), and death risk rose with cancer stage (HR = 2.375, 95% CI = 1.499 - 3.762, P = 0.00058). Despite immune evasion in high-PIP5K1B tumors, they were sensitive to bleomycin (P < 0.001, R2 = 0.06) and docetaxel (P < 0.001, R2 = 0.21). DISCUSSION: The study's findings underscore the potential of PIP5K1B as a prognostic biomarker and therapeutic target in gastric cancer, opening up new possibilities for personalized treatment approaches. CONCLUSION: Integrating pan-cancer multi-omics data, we found PIP5K1B serves as a significant prognostic biomarker in STAD, with its high expression linked to poor survival outcomes. Its expression in tumor - associated myofibroblasts and involvement in antigen processing suggest a complex role in the tumor immune landscape. Furthermore, the sensitivity of high - PIP5K1B tumors to specific chemotherapies offers new avenues for targeted treatment strategies in STAD.