Risk Signature Related to Immunotherapy Reaction of Hepatocellular Carcinoma Based on the Immune-Related Genes Associated With CD8+ T Cell Infiltration

Abstract

Background: Hepatocellular carcinoma (HCC) is the most common histological type of liver cancer, with an unsatisfactory long-term survival rate. Despite immune checkpoint inhibitors for HCC have got glories in recent clinical trials, the relatively low response rate is still a thorny problem. Therefore, there is an urgent need to screen biomarkers of HCC to predict the prognosis and efficacy of immunotherapy.Methods: Gene expression profiles of HCC were retrieved from TCGA, GEO, and ICGC databases while the immune-related genes (IRGs) were retrieved from the ImmPort database. CIBERSORT and WGCNA algorithms were combined to identify the gene module most related to CD8+ T cells in the GEO cohort. Subsequently, the genes in hub modules were subjected to univariate, LASSO, and multivariate Cox regression analyses in the TCGA cohort to develop a risk signature. Afterward, the accuracy of the risk signature was validated by the ICGC cohort, and its relationships with CD8+ T cell infiltration and PDL1 expression were explored.Results: Nine IRGs were finally incorporated into a risk signature. Patients in the high-risk group had a poorer prognosis than those in the low-risk group. Confirmed by TCGA and ICGC cohorts, the risk signature possessed a relatively high accuracy. Additionally, the risk signature was demonstrated as an independent prognostic factor and closely related to the CD8+ T cell infiltration and PDL1 expression.Conclusion: A risk signature was constructed to predict the prognosis of HCC patients and detect patients who may have a higher positive response rate to immune checkpoint inhibitors.

Comprehensive analysis of anoikis‐related lncRNAs for predicting prognosis and response of immunotherapy in hepatocellular carcinoma

“…For now, many HCC‐specific prognostic signatures have been constructed by bioinformatic analysis [ 26 , 27 ]. Although several prognostic models based on anoikis‐related genes for HCC have been established, signatures with anoikis‐related lncRNAs have not been identified [ 28 , 29 ].…”

STING pathway contributes to the prognosis of hepatocellular carcinoma and identification of prognostic gene signatures correlated to tumor microenvironment

“…Now, several anti-PD-1 antibodies have been approved by the Food and Drug Administration (FDA) such as nivolumab which was permitted to treat patients with advanced HCC for the second-line approach, and pembrolizumab which was also favored to use in the patients diagnosed at advanced stages [ 9 , 10 ]. Moreover, a recent clinical trial targeting unresectable HCC composed of atezolizumab (anti-PD-L1) and bevacizumab (anti-VEGF) reported that increased overall survival (OS) and progression-free survival (PFS) were observed in the combined group than sorafenib alone group [ 11 ].…”