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Research Article: Unraveling the role of PPFIA1 in cancer: a comprehensive multi-omics analysis and functional validation from pan-cancer to pancreatic cancer

Date Published: 2026-07-08

Abstract:
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. 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 . 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. 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.

Introduction:
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.

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