Rongbin Gong,1,* Moqin Qiu,2,* Yingchun Liu,1,3 Ji Cao,4 Zihan Zhou,4 Qiuling Lin,5 Yanji Jiang,6 Xiumei Liang,7 Yuying Wei,1 Qiuping Wen,1 Peiqin Chen,1 Xiaoxia Wei,5 Junjie Wei,1 Shicheng Zhan,1 Ruoxin Zhang,8 Dong Ye,9 Hongping Yu1,3,10 

1Department of Experimental Research, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 2Department of Respiratory Oncology, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 3Key Cultivated Laboratory of Cancer Molecular Medicine of Guangxi Health Commission, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 4Department of Cancer Prevention and Control, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 5Department of Clinical Research, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 6Department of Scientific Research, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 7Department of Disease Process Management, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 8School of Public Health, Key Laboratory of Public Health Safety, Ministry of Education, Fudan University, Shanghai, People’s Republic of China; 9Department of Integrated Medicine, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 10Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Hongping Yu, Email yuhongping@stu.gxmu.edu.cn Dong Ye, Email ndefylxy@163.com

Purpose: 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.
Methods: 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.
Results: We found that UGP2 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, P < 0.001], and that FBP2 rs635087 G allele was significantly associated with a worse OS in these patients (HR = 1.38, 95% CI = 1.18– 1.61, P < 0.001). The expression quantitative trait loci analysis using the GTEx database showed that the rs635087 G allele was significantly correlated with reduced FBP2 mRNA expression levels in normal liver tissues (P < 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 UGP2 and FBP2 were significantly lower in HCC tissues than in normal liver tissues (both P < 0.001), and high expression levels of both UGP2 and FBP2 were significantly associated with favorable survival in HCC patients (both P < 0.001).
Discussion: Our findings suggested that genetic variants in glycolysis pathway genes may serve as novel prognostic markers for survival of patients with HBV-HCC, especially FBP2 rs635087, if validated in additional larger studies and functional investigations.

Keywords: glycolysis, hepatitis B virus, hepatocellular carcinoma, single nucleotide polymorphism, over survival