Zhuomin Lyu1, Yibing Chen2, Xu Guo2, Feng Zhou3, Zhaoyong Yan1, Jinliang Xing2, Jiaze An4, Hongxin Zhang5. 1. Department of Pain Treatment, Tangdu Hospital, Fourth Military Medical University, 169, Changle West Road, Xi'an, Shaanxi, 710038, China. 2. State Key Laboratory of Cancer Biology, Experimental Teaching Center of Basic Medicine, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China. 3. Department of General Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China. 4. Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, 169, Changle West Road, Xi'an, Shaanxi, 710032, China. Electronic address: anchen@fmmu.edu.cn. 5. Department of Pain Treatment, Tangdu Hospital, Fourth Military Medical University, 169, Changle West Road, Xi'an, Shaanxi, 710038, China. Electronic address: zhhxtdjr@163.com.
Abstract
BACKGROUND: Metabolic reprogramming is an important hallmark of cancer cells, including the alterations of activity and expression of enzymes in glucose metabolism. Previous studies have demonstrated the critical role of glucise-6-phosphate isomerase (GPI) in cancer initiation, metastasis and progression. However, the significance of single nucleotide polymorphisms (SNPs) in GPI gene has not been investigated in hepatocellular carcinoma (HCC). METHODS: In this study, a total of 3 functional SNPs in GPI gene were genotyped in 492 HCC patients with surgical treatment. Multivariate Cox proportional hazards model and Kaplan-Meier curve were used for the analysis of overall survival (OS) and recurrence-free survival (RFS). RESULTS: The homozygous variant genotypes of rs7248411 in mRNA splice sites of GPI gene were significantly associated with an increased risk of death in the multivariate analysis (Hazard ratio [HR], 2.07; 95% confidence interval [95% CI]: 1.16-3.68 in a recessive model). In stratified analysis, the association remained significant in patients with high α-fetal protein (AFP) level (HR=2.37, 95% CI 1.25-4.49). Moreover, we identified the interaction between rs7248411 and AFP level in predicting the prognosis of HCC patients (P for interaction<0.001). CONCLUSIONS: Our data suggest that GPI gene polymorphism may serve as potential biomarkers to predict the OS of HCC. Further studies with different ethnicities are needed to validate our findings and generalize its clinical utility. Copyright Â
BACKGROUND: Metabolic reprogramming is an important hallmark of cancer cells, including the alterations of activity and expression of enzymes in glucose metabolism. Previous studies have demonstrated the critical role of glucise-6-phosphate isomerase (GPI) in cancer initiation, metastasis and progression. However, the significance of single nucleotide polymorphisms (SNPs) in GPI gene has not been investigated in hepatocellular carcinoma (HCC). METHODS: In this study, a total of 3 functional SNPs in GPI gene were genotyped in 492 HCCpatients with surgical treatment. Multivariate Cox proportional hazards model and Kaplan-Meier curve were used for the analysis of overall survival (OS) and recurrence-free survival (RFS). RESULTS: The homozygous variant genotypes of rs7248411 in mRNA splice sites of GPI gene were significantly associated with an increased risk of death in the multivariate analysis (Hazard ratio [HR], 2.07; 95% confidence interval [95% CI]: 1.16-3.68 in a recessive model). In stratified analysis, the association remained significant in patients with high α-fetal protein (AFP) level (HR=2.37, 95% CI 1.25-4.49). Moreover, we identified the interaction between rs7248411 and AFP level in predicting the prognosis of HCCpatients (P for interaction<0.001). CONCLUSIONS: Our data suggest that GPI gene polymorphism may serve as potential biomarkers to predict the OS of HCC. Further studies with different ethnicities are needed to validate our findings and generalize its clinical utility. Copyright Â
Authors: Nissar Ahmad Wani; Bo Zhang; Kun-Yu Teng; Juan M Barajas; Tasneem Motiwala; Peng Hu; Lianbo Yu; Rafael Brüschweiler; Kalpana Ghoshal; Samson T Jacob Journal: Mol Cancer Res Date: 2017-11-29 Impact factor: 5.852