A Novel Gene Signature Associated with Inflammatory Responses and Immune Status Assists in Prognosis and Intervention for Patients with HCC.

Abstract

Tumor growth depends on tumor cells and the tumor microenvironment, which are regulated by inflammation and immune responses. However, the roles of inflammation and immune status in hepatocellular carcinoma (HCC) remain unclear. The aim of this study was to evaluate the prognostic value of an inflammatory response- related gene signature associated with immune status, which may provide insight into new treatment options for HCC patients. Differentially expressed genes associated with inflammation were obtained from The Cancer Genome Atlas (TCGA), the Gene Expression Omnibus, and the Molecular Signatures Database. An inflammation-associated prognostic gene signature was constructed and validated using TCGA and the International Cancer Genome Consortium datasets, respectively, using LASSO Cox regression analysis. Log-rank was performed to compare the overall survival of low- and high-risk score cohorts. Immune cell infiltration and immune-related functions were analyzed using single-sample gene enrichment analysis. The structures of the drugs identified by the prognostic model were predicted using PubChem. The drugs sensitivity of bleomycin, simvastatin and zoledronate detected by CCK8 colorimetric assay. The mRNA levels of 7 genes in HCC after drug treatment analyzed via qRT-PCR. Inflammation-associated genes, including ITGA5, MEP1A, P2RX4, RIPK2, SLC7A1 and SRI, were identified and found to be associated with the prognosis of HCC. We further found that the high-risk patients experienced poor prognosis, which was observed to be an independent and significant risk factor for prognosis. Moreover, we observed elevated expression levels in multiple immune cell types and immune function. Lastly, we validated that bleomycin, simvastatin and zoledronate could regulate these genes in HCC. The inflammatory-response-associated gene signature could predict the prognosis and the immunological status of HCC patients. Additionally, bleomycin, simvastatin and zoledronate may represent potential drug candidates that could inhibit these genes. This may constitute a new approach for the treatment of HCC.