Research Paper|Volume 13, Issue 6|pp 8563—8587

A novel panel based on immune infiltration and tumor mutational burden for prognostic prediction in hepatocellular carcinoma

Chan Xie¹, Hewei Wu¹, Tao Pan², Xingrong Zheng¹, Xiaoan Yang¹, Genglin Zhang¹, Yunwen Lian¹, Jiaxin Lin¹, Liang Peng¹

¹Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China
²Department of Interventional Radiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China

* Equal contribution

Received: May 27, 2020Accepted: October 31, 2020Published: March 10, 2021

https://doi.org/10.18632/aging.202670

Copyright: © 2021 Xie 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

Tumor mutation burden (TMB) has been associated with prognosis in various malignancies, but it has yet to be elucidated in hepatocellular carcinoma (HCC). We aimed to investigate the prognostic effects of TMB and its relationship with immune infiltration through multiple databases and whole-exome sequencing, so as to establish a panel model capable of predicting prognosis. The results demonstrated that the prognosis of high TMB group was worse than that of low TMB group, with a cutoff TMB value of 4.9. Enrichment analysis demonstrated that differentially expressed genes were mainly related to T cell activation, cell membrane localization and matrix composition. Tumor immune infiltration analysis revealed the infiltrations of Th2, Th17, and Tgd were up-regulated in high TMB group, while those of Tr1, MAIT, and DC were up-regulated in low TMB group. TMB-Infiltration model fit well with the actual survival observation, with a C-index 0.785 (0.700-0.870), which verified in ICGC-LIRI-JP was 0.650 (0.553-0.747). Additionally, these screened immune genes performed well in predicting tumor vascular invasion with a C-index of 0.847 (0.778-0.916). Overall, these results indicated that patients with high mutation frequency of immune-related genes and high TMB were prone to have worse prognosis and relapse after radical treatment.