Tumor mutation burden associated with miRNA-gene interaction outcome mediates the survival of patients with liver hepatocellular carcinoma

Qing-Jiang Yu; Yi-Zhi Liang; Xiao-Ping Mei; Tai-Yong Fang

doi:10.17179/excli2020-1224

Tumor mutation burden associated with miRNA-gene interaction outcome mediates the survival of patients with liver hepatocellular carcinoma

EXCLI J. 2020 Jun 22:19:861-871. doi: 10.17179/excli2020-1224. eCollection 2020.

Authors

Qing-Jiang Yu¹, Yi-Zhi Liang², Xiao-Ping Mei¹, Tai-Yong Fang²

Affiliations

¹ Department of Hepatobiliary Surgery, First Affiliated Hospital of Jiaxing University, Jiaxing 314000, China.
² Department of Gastroenterology, Second Affiliated Hospital, Fujian Medical University, Quanzhou 362000, China.

Abstract

Tumor mutation burden (TMB) is associated with immunogenic responses and the survival of cancer patients. This study demonstrates how TMB levels impact the immune-related cells, genes, and miRNAs, and how miRNA/gene interactions respond to variations in the survival rate of patients with liver hepatocellular carcinoma (LIHC). LIHC patients were divided into two groups, either a low TMB (< median) or a high TMB (≥ median) group. We found that high TMB plays a positive role in immune-mediated infiltration, generating more CD4 T-cells and memory B cells. Among the 21 immune genes that altered significantly, only C9orf24 and CYP1A1 were expected to up-regulate in LIHC patients with high TMB. A total of 19 miRNAs, which regulate various functional pathways, were significantly altered in patients with LIHC. One of the miRNA/gene pair, hsa-miR-33a/ALDH1A3 was significantly associated with the survival rate of LIHC patients. Our results suggest that LIHC patients with high TMB can be treated more effectively with immunotherapy.

Keywords: liver hepatocellular carcinoma (LIHC); miRNA-gene interaction; prognosis; tumor mutation burden (TMB).