Research Paper Volume 12, Issue 12 pp 12187—12205
Identification of immunological subtypes of hepatocellular carcinoma with expression profiling of immune-modulating genes
- 1 State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China
- 2 Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China
- 3 Precision Medicine Institute, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
Received: January 9, 2020 Accepted: May 20, 2020 Published: June 16, 2020
https://doi.org/10.18632/aging.103395How to Cite
Copyright © 2020 Cao et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Recent studies demonstrate that immune checkpoint inhibitor (ICI) therapy has achieved success in many types of advanced cancers including advanced hepatocellular carcinoma (HCC). However, ICI therapy is beneficial in only some HCC patients, suggesting that immune-responses are highly variable in HCCs. Therefore, understanding the immune status in HCC microenvironment will facilitate ICI immunotherapy and guide patient selection for the therapy. In this study, we first analyzed the expression profile of immune-modulating genes and their relationship with survival of HCC patients using the data downloaded from The Cancer Genome Atlas - Liver Hepatocellular Carcinoma (TCGA-LIHC) database, and found that the higher expressions of CD276 (B7-H3) and CD47 were significantly associated with poor survival. Then we identified 4 immune subtypes of HCCs with different survivals by using the combination expression of B7-H3 (or CD47) and CD8. Patients with B7-H3low/CD8high or CD47low/CD8high have the best survival while ones with B7-H3high/CD8low or CD47high/CD8low have the worst survival. The 4 immune subtypes were validated in another 72 HCC patients obtained from South China. In conclusion, our findings suggest that HCC patient prognosis is associated with immunophenotypes by T cell infiltration (CD8 expression) and the expression of the adaptive immune resistance gene (B7-H3 or CD47), and this immune classification system will facilitate HCC patient selection for ICI immunotherapy.