Genetic Variants in M5C Modification Genes Are Associated with Survival of Patients with HBV-related Hepatocellular Carcinoma

Overview

Journal Arch Toxicol

Specialty Toxicology

Date 2024 Mar 4

PMID 38438738

Authors

Bowen Chen

Moqin Qiu

Rongbin Gong

Yingchun Liu

Zihan Zhou

Qiuping Wen

XiaoXia Wei

Xiumei Liang

Yanji Jiang

Peiqin Chen

Yuying Wei

Qiongguang Huang

Qiuyan Mo

Qiuling Lin

Hongping Yu

Affiliations

Soon will be listed here.

Abstract

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with a high mortality rate. The 5-methylcytosine (m5C), a type of RNA modification, plays crucial regulatory roles in HCC carcinogenesis, metastasis, and prognosis. However, a few studies have investigated the effect of genetic variants in m5C modification genes on survival of patients with hepatitis B virus (HBV)-related HCC. In the present study, we evaluated associations between 144 SNPs in 15 m5C modification genes and overall survival (OS) in 866 patients with the HBV-related HCC. Expression quantitative trait loci (eQTL) analysis and differential expression analysis were conducted to investigate biological mechanisms. As a result, we identified that two SNPs (NSUN7 rs2437325 A > G and TRDMT1 rs34434809 G > C) were significantly associated with HBV-related HCC OS with adjusted allelic hazards ratios of 1.25 (95% confidence interval = 1.05-1.48 and P = 0.011) and 1.19 (1.02-1.38 and P = 0.027), respectively, with a trend of combined risk genotypes (P < 0.001). Moreover, the results of eQTL analyses showed that both NSUN7 rs2437325 G and TRDMT1 rs34434809 C alleles were associated with a reduced mRNA expression level in 208 normal liver tissues (P = 0.007 and P < 0.001, respectively). Taken together, genetic variants in the m5C modification genes may be potential prognostic biomarkers of HBV-related HCC after hepatectomy, likely through mediating the mRNA expression of corresponding genes.

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