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
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.