Exploration of key genes combining with immune infiltration level and tumor mutational burden in hepatocellular carcinoma

Abstract Background: Hepatocellular carcinoma (HCC) is the second most common cancer-associated cause of death globally. It is thus vital that the novel diagnostic and prognostic biomarkers associated with early-stage HCC be identified. Keratin 17 (KRT17) has previously been reported to be associated with certain cancer types. However, its relationship with HCC remains to be defined. Methods: The expression of KRT17 in the TCGA LIHC database and in 44 pairs of samples collected from patients with HCC was assessed using qRT-PCR, WB, and IHC. The prognostic relevance of KRT17 was assessed using Kaplan–Meir curves. The important cancer- and KRT17-related biological processes were defined through gene set enrichment analysis (GSEA). The functional link between KRT17 expression and tumor cell proliferation/survival was assessed using flow cytometry, colony formation assay, CCK-8 assay, and subcutaneous tumor model approaches. Protein–protein interaction (PPI) networks and analyses of immune cell infiltration were also employed to define the signaling pathways associated with KRT17 expression in HCC. Results: HCC tissue samples exhibited increased KRT17 mRNA and protein expression that was predictive of poorer patient survival (P <0.001). GSEA and functional experiments revealed that KRT17 functioned as a regulator of HCC. PPI network analyses also revealed that KRT17 expression was linked to immune cell infiltration and activation in patients with HCC. Conclusions: We found that increased KRT17 levels were associated with poorer survival, more aggressive disease, and altered immune cell infiltration in patients suffering from HCC. KRT17 may function as an oncogene and a prognostic biomarker in this cancer type.