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.
Highlights
Hepatocellular carcinoma (HCC) is the third most common digestive cancer in global incidence, and mortality ranks the fourth highest among all tumors
Tumor immune infiltration analysis revealed the infiltrations of Type 2 T helper cells (Th2), Type 17 T helper cells (Th17), and Gamma-delta T cells (Tgd) were upregulated in high Tumor mutation burden (TMB) group, while those of type 1 regulatory cells (Tr1), Mucosal-associated invariant T cells (MAIT), and Dendritic cells (DC) were up-regulated in low TMB group
TMB-high Infiltrating (IF) fit well with the actual survival observation, with a Concordance index (C-index) 0.785 (0.700-0.870), which verified in International Cancer Genome Consortium. area under the curve (AUC) (ICGC)-LIRI-JP was 0.670 (0.573-0.767), and 0.774 (0.670-0.877) in GSE76427
Summary
Hepatocellular carcinoma (HCC) is the third most common digestive cancer in global incidence, and mortality ranks the fourth highest among all tumors. Rates of both incidence and mortality in men are 2 to 3 times higher than women. The mortality of HCC ranks second only to that of lung cancer among men [1]. The pace of increasing in woman has slowed from previous years, incidence in men has continued to grow at a rate of 2% to 3% annually for the past decade[2]. Tumor mutation burden (TMB) was associated with prognosis in various malignancies, but it remains to be elucidated in hepatocellular carcinoma (HCC). We aimed to investigate the prognostic effects of TMB and its relationship with immune infiltration so as to establish a panel model capable of predicting prognosis
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