Correlation analysis of tumor mutation burden of hepatocellular carcinoma based on data mining

Weijie Zhou; Dalang Fang; Yongfei He; Jie Wei

doi:10.21037/jgo-21-259

Correlation analysis of tumor mutation burden of hepatocellular carcinoma based on data mining

J Gastrointest Oncol. 2021 Jun;12(3):1117-1131. doi: 10.21037/jgo-21-259.

Authors

Weijie Zhou¹, Dalang Fang², Yongfei He³, Jie Wei¹

Affiliations

¹ Department of Hematology, Baise People's Hospital, Baise, China.
² Department of Breast and Thyroid Surgery, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China.
³ Department of Hepatobiliary Surgery, the First Affiliated Hospital of Guangxi Medical University, Guangxi, China.

Abstract

Background: The aim of this study was to determine the relationship between tumor mutation burden (TMB) and prognosis of patients with hepatocellular carcinoma (HCC), and to explore the differential expression of genes in HCC by TMB and the relationship between immune cells, TMB, and HCC.

Methods: Somatic variation data, gene transcriptional expression data and clinical information of patients with HCC were obtained from cancer genome map (TCGA) database. Analyze the characteristics of the gene mutation data of the sample, divide the high and low TMB groups and draw the survival curve at the same time, carry on the difference analysis to the gene of TMB, further carry on the univariate Cox regression analysis and Lasso regression analysis and construct the clinical model. Download the dataset GSE14520, from the Gene Expression Omnibus (GEO) database to verify the genes of the prognostic model. The differential genes were analyzed by gene ontology (GO) enrichment analysis and Kyoto encyclopedia of genes and genomes by (KEGG) enrichment analysis. Then the relative abundance of 22 immune cell types in HCC and normal control samples was calculated. Finally, the correlation between the scores of immune cells and Risk model was analyzed.

Results: Tumor protein p53 (TP53), catenin1 (CTNNB1), titin (TTN), mucin 16 (MUC16), and albumin (ALB) are the most common top 5 mutations in HCC. The prognosis of high level TMB group is worse than that of low TMB group. A total of 122 differentially expressed genes were screened by differential analysis of TMB genes. SQSTM1, ME1, BAMBI and PTTG1 are independent risk factors for poor prognosis of HCC. GO and KEGG analysis showed that the differential genes were mainly in extracellular matrix and immune response. There were significant differences in the distribution of Macrophages M0 and T cells CD4 native cells between HCC and normal tissues, which were correlated with the differential genes of TMB and correlated with prognosis.

Conclusions: There is a negative correlation between TMB and the prognosis of patients with HCC. TMB has an effect on the differential expression of genes in HCC cells and the distribution of immune cells in tumor tissues.

Keywords: Hepatocellular carcinoma (HCC); immune, prognosis; tumor mutation burden (TMB).