Exploration of the correlation between AHNAK2 and pancreatic cancer and its role in the tumor microenvironment based on bioinformatics: Computational pharmacology

Pancreatic adenocarcinoma (PAAD) ranks as a leading global cause of cancer-related mortality. Current standard treatments, including surgery, radiotherapy, and chemotherapy, offer limited survival advantages to patients. Immunotherapy, which has achieved remarkable success in prolonging overall survival (OS) in lung cancer patients, has yet to reach its full potential in PAAD. Only a subset of patients responded to immunotherapy, highlighting the urgent need to identify reliable immunotherapy biomarkers for better patient selection. To unearth immune prognosis-associated genes in PAAD, we harnessed R software and the TIMER database to retrieve raw data from The Cancer Genome Atlas and Gene Expression Omnibus. The expression patterns of target genes were comprehensively analyzed across The Cancer Genome Atlas and Gene Expression Omnibus datasets. R software and the TISIDB database were utilized for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. Additionally, correlations with tumor immune profiles were explored. Through this systematic screening, we identified AHNAK Nucleoprotein 2 (AHNAK2) as a promising immune prognosis-related gene. AHNAK2 exhibits significant differential expression between PAAD and normal tissues, positioning it as a valuable biomarker for PAAD diagnosis and prognosis assessment. Enrichment analysis reveals that differential genes related to AHNAK2 are predominantly involved in epidermis development, keratinization, intermediate filament organization, and epithelial cell differentiation. Notably, AHNAK2 expression positively correlates with the infiltration levels of memory B cells (r = 0.17, P < .05), regulatory T cells (Tregs) (r = 0.21, P < .001), and macrophages (r = 0.35, P < .001). Drug susceptibility analysis further demonstrates that AHNAK2 confers significant resistance to bafetinib (r = -0.38, P < .05) and curcumin (r = -0.55, P < .05). Our study provides compelling evidence of a robust association between AHNAK2, the prognosis of PAAD, and the tumor immune microenvironment. The findings underscore the potential of AHNAK2 to serve as a valuable biomarker for immunotherapy in PAAD. This discovery paves the way for the development of more tailored and efficacious treatment approaches, offering new prospects for improving patient outcomes and advancing the field of PAAD management.