Unveiling PIK3CA mutation: a prognostic beacon in endometrial carcinoma and its immune implications

Endometrial carcinoma (EC) is a prevalent gynecological malignancy with diverse genetic underpinnings. This study aimed to elucidate the prognostic significance of genetic mutations, particularly PIK3CA, and their impact on immune landscape and therapeutic outcomes in EC.

Clinical and RNAseq data were acquired from cBioPortal and The Cancer Genome Atlas (TCGA). These data were utilized for prognostic analysis. Immune landscape analysis using single sample Gene Set Enrichment Analysis (ssGSEA) revealed enhanced infiltration of immune cells in PIK3CA-mutated samples. A PIK3CA-related risk model was constructed using least absolute shrinkage and selection operator (LASSO) regression. A nomogram was used the results derived from Cox univariate regression analysis.

We identified PIK3CA mutation significantly correlating with improved overall survival (OS). Immune landscape analysis suggested an activated immune state. Differential expression analysis identified 50 differentially expressed genes (DEGs), predominantly upregulated in the mutant group, with enrichment in immune-related pathways, particularly B cell functions. Furthermore, PIK3CA mutation was associated with higher tumor mutational burden (TMB) and distinct immune profiles, potentially enhancing responsiveness to immunotherapy. A PIK3CA-related risk model identified three key genes (IGHA1, CRABP1, and SST) associated with survival outcomes. Finally, the nomogram was helpful to predict the prognosis of patients with EC.

Our study highlighted the potential of PIK3CA mutation as a biomarker for stratifying EC patients and tailoring therapeutic strategies, particularly in the context of immune checkpoint inhibitors. Future research should focus on elucidating the mechanistic role of PIK3CA in EC pathogenesis and its interaction with the tumor microenvironment (TME) to optimize patient outcomes.