Abstract

Background Colorectal adenocarcinoma (COAD) is a leading cause of cancer-related death globally, necessitating the identification of new molecular drivers and therapeutic targets. Keratin 80 (KRT80) is an intermediate filament protein whose dysregulation has been linked to malignancy in various cancers, yet its role in COAD pathogenesis is poorly understood. Given the critical need to understand COAD progression, this study was designed to determine the expression and prognostic significance of KRT80 in COAD, its impact on the tumor immune microenvironment, and its functional effects on cancer cell proliferation, migration, and invasion, along with the potential signaling pathways involved. Methods KRT80 expression and its prognostic value in COAD were analyzed using TIMER database, UALCAN database, GEPIA database, and Kaplan-Meier plotter. Immune cell infiltration was evaluated via CIBERSORT and single-sample gene set enrichment analysis (ssGSEA). Somatic mutations were analyzed from The Cancer Genome Atlas (TCGA) data. Functional enrichment analysis [Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, gene set enrichment analysis (GSEA)] was performed on KRT80-associated genes. In vitro, KRT80 protein levels were examined in COAD cell lines by Western blot (WB). Stable knockdown and overexpression models were created. Functional assays [Cell Counting Kit-8 (CCK-8), Transwell, wound healing] assessed proliferation, migration, and invasion. WB measured STAT3 pathway activity. Results KRT80 was significantly overexpressed in COAD tissues and high expression correlated with poorer overall, first progression, and post-progression survival (PPS). KRT80 expression positively correlated with M0 macrophage and activated mast cell infiltration, and negatively with resting memory CD4+ T cells and naive B cells.