AUTHOR=Zou Yiping , Chen Zhihong , Han Hongwei , Ruan Shiye , Jin Liang , Zhang Yuanpeng , Chen Zhengrong , Ma Zuyi , Lou Qi , Shi Ning , Jin Haosheng
TITLE=Risk Signature Related to Immunotherapy Reaction of Hepatocellular Carcinoma Based on the Immune-Related Genes Associated With CD8+ T Cell Infiltration
JOURNAL=Frontiers in Molecular Biosciences
VOLUME=8
YEAR=2021
URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2021.602227
DOI=10.3389/fmolb.2021.602227
ISSN=2296-889X
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.