Correlations analysis between HCC mutation burden and patients’ prognosis based on data mining

Objective To study the correlations between tumor mutation burden (TMB) and the prognosis of hepatocellular carcinoma (HCC) patients, and to investigate the effect of TMB on differential expression genes of HCC and the proportion of invasive immune cells in tumor tissues. Methods The somatic variation data, gene transcriptional expression data and clinical information of HCC patients were obtained from the cancer genome atlas (TCGA) database. The R program language (version 3.6.1) maftools function package was used to analyze the gene mutation data characteristics of the samples. The TMB value of each sample was calculated using the full-exon sequencing data of patients with hepatocellular carcinoma on the VarScan2 platform, sorted by TMB value, and the median value was used to divide all samples into high TMB and low TMB groups. Kaplan-Meier method was used to draw the survival curves of two groups of patients and log-rank test was performed to determine the correlation between tumor mutation load and prognosis. The Limma function package of R language was used to screen the differentially expressed genes between the two groups (FDR=0.05 and logFC=1), and the clusterProfiler function package of R language was used to perform gene ontology (GO) enrichment analysis of the differential genes and kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis (screening criteria were all P<0.05). Then the CIBERSORT tool was used to compare and analyze the difference in the proportion of invasive immune cells between the two groups. Results A total of 364 patients with HCC from TCGA database were included in the study. Mutations were found in 327(84%) samples, and there was a synergistic correlation between OBSCN and FLG mutations (P 0.05). A total of 198 with differentially expressed genes (28 up-regulated genes and 170 down-regulated genes) were screened between the high TMB group and the low TMB group. In GO analysis, it was found that the differentially expressed genes were mainly enriched in extracellular matrix tissues, extracellular structural tissues, extracellular matrix, extracellular matrix containing collagen, extracellular matrix structural components and other functions. In KEGG analysis, differential genes were highly enriched in extracellular matrix receptor interaction pathway and adhesive plaque pathway. In the correlation analysis of the proportion of infiltrating immune cells, CD4+ memory T cells were more infiltrating in the low TMB group (P<0.05). Monocytes showed a higher degree of infiltration in the high TMB group (P<0.05). Conclusion There was no correlation between TMB and the prognosis of HCC patients. TMB has significant influence on the differential expression genes of HCC and the proportion of invasive immune cells in tumor tissues. Key words: Carcinoma, hepatocellular; Tumor mutation burden; Prognosis