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

Yiping Zou; Zhihong Chen; Hongwei Han; Shiye Ruan; Liang Jin; Yuanpeng Zhang; Zhengrong Chen; Zuyi Ma; Qi Lou; Ning Shi; Haosheng Jin

doi:10.3389/fmolb.2021.602227

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

Front Mol Biosci. 2021 Mar 19:8:602227. doi: 10.3389/fmolb.2021.602227. eCollection 2021.

Authors

Yiping Zou^{1

2}, Zhihong Chen^{1

2}, Hongwei Han^{1

3}, Shiye Ruan¹, Liang Jin¹, Yuanpeng Zhang¹, Zhengrong Chen¹, Zuyi Ma^{1

2}, Qi Lou^{1

3}, Ning Shi¹, Haosheng Jin¹

Affiliations

¹ Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
² College of Medicine, Shantou University, Shantou, China.
³ The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China.

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.

Keywords: CD8+ T cell; hepatocellular carcinoma; immune checkpoint inhibitors; immune-related genes; prognosis.