Immunosenescence-Related Gene MAFF is Involved in Immune Regulation and Malignant Progression in Pancreatic Adenocarcinoma.

Abstract

Immunosenescence has lately become a focal point in oncology investigations. Nevertheless, its significance in pancreatic adenocarcinoma (PAAD) remains to be elucidated. This research sought to examine the predictive value and treatment implications of immunosenescence-related genes in PAAD. We use the public datasets from TCGA and GEO to extract clinicopathological factors and RNA-sequencing data. Differentially expressed genes (DEGs) were ascertained, and then molecular subtypes were classified by consensus clustering. Functional enrichment analysis using KEGG and GO, GSEA, survival analysis, and the design of an immunosenescence-linked risk signature using Lasso-Cox regression is part of the analytical approach. We used TIMER, TISCH, etc., to further elaborate its relationship with the tumor immune microenvironment. Drug sensitivity analysis is conducted using GSCA. The independent prognostic gene MAFF's expression was validated utilizing GEPIA2, real-time quantitative PCR (RT-qPCR), and western blot (WB). We identify two immunosenescence-associated subtypes of PAADwith distinct gene expression profiles and clinical outcomes. The creation of a risk signature model utilizing IMSRGs reveals three genes-NCAM1, SESN1, and MAFF-that are significantly correlated with overall survival. The elevated-risk cohort, as identified by the risk assessment metric, correlates with poorer survival rates. Additionally, we uncover an association between the risk indicator and the tumor milieu, encompassing immune cell infiltration patterns and drug sensitivity profiles. Our results and published data show that MAFF levels in pancreatic cancer tissues markedly exceeds that of normal tissues and have a bad effect on prognosis. The study identifies a prognostic gene signature for PAAD, revealing its potential in personalized medicine and immunotherapy, and highlights the role of immunosenescence in cancer treatment.