Genetic variants in m5C modification genes are associated with survival of patients with HBV-related hepatocellular carcinoma

期刊论文
发表日期：

2024年3月4日

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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

摘要

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_trend < 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.