Comprehensive analysis of genomic and immunological profiles in Chinese and Western hepatocellular carcinoma populations

Abstract

In this study, we explored the genomic and immune cell infiltration profiles among four distinct Hepatocellular carcinoma (HCC) types. This study included 100 patients (all tumors and adjacent liver tissues received WES sequencing) with HCC from the West China Hospital (WCH) and patients were divided into WCH-HBV-HCC group and WCH-NonHBV-HCC group. Additionally, this study included 106 HBV-related HCC (TCGA-HBV-HCC) and 69 alcoholic HCC (TCGA-Alcol-HCC) patients from the TCGA. We analyzed the high-frequency gene mutation, copy number variation (CNV), mutation spectrum, signatures and immune cell infiltration of these four groups. This study showed significant differences in gene mutation and CNV level among four HCC groups. Compared to genomic level, there is no significant difference between TCGA-HBV-HCC and TCGA-Alcol-HCC groups in fractions of tumor-infiltrating immune cells. According to the status of immune cell infiltration, patients were classified into immune-HIGH, immune-MIX and immune-LOW group, respectively. In the WCH-HBV-HCC and TCGA-HBV-HCC groups, more patients in the Immune-LOW group had TP53 mutation. Except for TP53, neither the other gene mutation nor tumor mutation burden was found to be associated with immune cell infiltration in the WCH-HBV-HCC, TCGA-HBV-HCC and TCGA-Alcol-HCC groups. In the CNV level, we found that samples with low immune infiltrate had higher number of deleted or amplified genes in the TCGA-HBV-HCC and TCGA-Alcol-HCC groups. We found comprehensive genomic heterogeneity among four HCC groups. The total gene CNV level, not the mutational burden of HCC, is associated with immune cell infiltration in HCC. TP53 mutation may injury the immune response of the HBV-related HCC.

Tumor Mutational Burden for Predicting Prognosis and Therapy Outcome of Hepatocellular Carcinoma

“…Many studies have investigated the relationship between TMB and the modulation of tumoral immunity. A WES analysis of tumoral and peritumoral tissues collected from 100 Chinese HCC patients and 175 HCC patients from the TCGA revealed that HBV-related HCC had a low immune cell infiltration and TP53 mutation, but TMB was not associated with immune infiltration in HBV- and alcoholic-related HCC patients of the TCGA cohort [ 78 ]. At variance, the level of copy number variation seemed to be more predictive of immune infiltration than TMB, even if a great heterogeneity among all the analyzed groups of HCC patients was observed.…”

Gill Junction Injury and Microbial Disorders Induced by Microcystin-Leucine Arginine in Lithobates catesbeianus Tadpoles

“…The gill mucosa is an important immune barrier, including innate and adaptive immunity [ 46 , 47 ]. Lysozyme is the widely distributed enzyme of the innate immune system that exhibits antibacterial activity [ 48 ].…”

Hepatocellular Carcinoma: Current Drug Therapeutic Status, Advances and Challenges

“…The approval of Lenvatinib in 2018 further solidified the role of kinase inhibitors (KIs) in the first-line treatment of advanced HCC. In a preclinical study, Sorafenib showed better antitumor activity in TP53 wild-type HCC, while Lenvatinib is more sensitive in HCCs with TP53 mutation [65,66]. However, the therapeutic effects of both drugs are far from satisfactory.…”