Unraveling the role of PPFIA1 in cancer: a comprehensive multi-omics analysis and functional validation from pan-cancer to pancreatic cancer
TL;DR
PPFIA1 emerges as a pan-cancer biomarker with prognostic significance and shows an oncogenic role in PAAD, potentially associating with EMT-related malignant phenotypes and warrants further investigation as a candidate biomarker and potential functional target for precision oncology.
Abstract
Background PTPRF interacting protein alpha 1 (PPFIA1), a cytoplasmic scaffold protein of the liprin family, modulates cell adhesion, signal transduction, and cytoskeletal dynamics. Its pan-cancer prognostic implications and functional roles, particularly in pancreatic cancer, remain underexplored. Methods Pan-cancer datasets including TCGA, GTEx and TISCH were integrated to assess PPFIA1 expression, genomic alterations, and pathway enrichment via Kaplan-Meier survival analysis, Cox regression, cBioPortal, and GSEA. In pancreatic cancer, external cohorts (e.g., GSE28735, GSE52452) were used for expression and prognosis validation. Besides, immunotherapy response was analyzed by using TIGER cohorts. Functional impacts were determined by using ShRNA-mediated knockdown in CFPAC-1, PANC-1 and Panc-02 cells and evaluating their proliferation, migration and invasion in vitro and in vivo. Results PPFIA1 exhibited differential expression across multiple cancer types, with overexpression in pancreatic adenocarcinoma (PAAD) versus non-tumor tissue at mRNA/protein levels, predominantly in malignant cells. High PPFIA1 correlated with adverse prognosis in PAAD across multiple endpoints. Genomic analyses revealed amplifications in head/neck cancers and mutations in endometrial carcinoma, clustering in SAM domains. GSEA enrichment analysis indicated pan-cancer activation of the mitotic spindle assembly pathway and Epithelial-Mesenchymal Transition (EMT) pathways in PAAD. Knockdown suppressed PAAD cell proliferation, colony formation, migration, invasion, and tumor growth in vivo. Notably, elevated PPFIA1 predicted superior responses to immunotherapy in pan-cancer cohorts rather than pancreatic cancer. Conclusions PPFIA1 emerges as a pan-cancer biomarker with prognostic significance and shows an oncogenic role in PAAD, potentially associating with EMT-related malignant phenotypes. Its association with immunotherapy efficacy suggests PPFIA1 warrants further investigation as a candidate biomarker and potential functional target for precision oncology.