Gong Rongbin, Qiu Moqin, Liu Yingchun, Cao Ji, Zhou Zihan, Lin Qiuling, Jiang Yanji, Liang Xiumei, Wei Yuying, Wen Qiuping, Chen Peiqin, Wei Xiaoxia, Wei Junjie, Zhan Shicheng, Zhang Ruoxin, Ye Dong, Yu Hongping
Department of Experimental Research, Guangxi Medical University Cancer Hospital, Nanning, People's Republic of China.
Department of Respiratory Oncology, Guangxi Medical University Cancer Hospital, Nanning, People's Republic of China.
J Hepatocell Carcinoma. 2025 Jun 7;12:1155-1166. doi: 10.2147/JHC.S492516. eCollection 2025.
Glycolysis is a group of metabolic processes that may alter tumor microenvironment to have effects on the growth and proliferation of tumor cells, including liver cancer. However, the effect of genetic variants in glycolysis pathway genes in survival of patients with hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) remains unclear.
We employed multivariable Cox proportional hazards regression analyses to estimate associations between genetic variants in 240 glycolysis pathway genes and overall survival (OS) of 866 patients with HBV-HCC, and we also used false positive report probability for multiple testing corrections.
We found that rs4293553 G allele was significantly associated with a better OS of HBV-HCC patients [hazards ratio (HR) = 0.73, 95% confidence interval (CI) = 0.62-0.86, < 0.001], and that rs635087 G allele was significantly associated with a worse OS in these patients (HR = 1.38, 95% CI = 1.18-1.61, < 0.001). The expression quantitative trait loci analysis using the GTEx database showed that the rs635087 G allele was significantly correlated with reduced mRNA expression levels in normal liver tissues ( < 0.001), but such a correlation was not significant for the rs4293553 G allele. Functional annotation results indicate that these two single nucleotide polymorphisms have potential biological functions, providing biological plausibility for the observed associations. In addition, the mRNA expression levels of both and were significantly lower in HCC tissues than in normal liver tissues (both < 0.001), and high expression levels of both and were significantly associated with favorable survival in HCC patients (both < 0.001).
Our findings suggested that genetic variants in glycolysis pathway genes may serve as novel prognostic markers for survival of patients with HBV-HCC, especially rs635087, if validated in additional larger studies and functional investigations.
糖酵解是一组代谢过程，可能会改变肿瘤微环境，从而影响肿瘤细胞（包括肝癌细胞）的生长和增殖。然而，糖酵解途径基因中的遗传变异对乙型肝炎病毒相关肝细胞癌（HBV-HCC）患者生存的影响仍不清楚。
我们采用多变量Cox比例风险回归分析来估计240个糖酵解途径基因中的遗传变异与866例HBV-HCC患者总生存期（OS）之间的关联，并且我们还使用了错误发现率进行多重检验校正。
我们发现rs4293553的G等位基因与HBV-HCC患者更好的总生存期显著相关[风险比（HR）=0.73，95%置信区间（CI）=0.62-0.86，P<0.001]，并且rs635087的G等位基因与这些患者更差的总生存期显著相关（HR=1.38，95%CI=1.18-1.61，P<0.001）。使用GTEx数据库进行的表达数量性状位点分析表明，rs635087的G等位基因与正常肝组织中mRNA表达水平降低显著相关（P<0.001），但rs4293553的G等位基因不存在这种显著相关性。功能注释结果表明这两个单核苷酸多态性具有潜在生物学功能，为观察到的关联提供了生物学合理性。此外，HCC组织中二者的mRNA表达水平均显著低于正常肝组织（均P<0.001），并且二者的高表达水平均与HCC患者的良好生存显著相关（均P<0.001）。
我们的研究结果表明，糖酵解途径基因中的遗传变异可能作为HBV-HCC患者生存的新型预后标志物，特别是rs635087，如果在更多更大规模的研究和功能研究中得到验证的话。
