Correlation of the differential expression of PIK3R1 and its spliced variant, p55α, in pan-cancer

PIK3R1, a regulatory subunit of class IA phosphoinositide-3-kinase (PI3K), undergoes alternative splicing to generate multiple isoforms, primarily p85α and p55α. The canonical isoform p85α associates with the catalytic subunit p110α to form the active PI3K complex, which regulates key cellular functions such as growth, proliferation, survival, and metabolism. In this study, we performed a comprehensive pan-cancer analysis integrating transcriptomic, proteomic, and genomic data to investigate the expression patterns of p85α and its splicing variant, p55α, and their associations with clinical outcomes. Our findings reveal that while p85α expression is significantly reduced, p55α is elevated in tumors as compared to normal samples. These alterations are linked to poor prognosis across multiple cancer types. Notably, we observed racial disparities in expression patterns, with African American patients exhibiting more pronounced downregulation of p85α and upregulation of p55α than European Americans, potentially contributing to differential clinical outcomes. This is the first study to systematically evaluate p85α and p55α expression across diverse cancers and populations, highlighting the role of alternative splicing in PI3K pathway dysregulation and its relevance to cancer progression and health disparities.