Genetic variants in glucose-6-phosphate isomerase gene as prognosis predictors in hepatocellular carcinoma.
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.
Department of Pain Treatment, Tangdu Hospital, Fourth Military Medical University, 169, Changle West Road, Xi'an, Shaanxi, 710038, China.
Zhuomin
Z
Lyu
State Key Laboratory of Cancer Biology, Experimental Teaching Center of Basic Medicine, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China.
Yibing
Y
Chen
State Key Laboratory of Cancer Biology, Experimental Teaching Center of Basic Medicine, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China.
Xu
X
Guo
Department of General Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China.
Feng
F
Zhou
Department of Pain Treatment, Tangdu Hospital, Fourth Military Medical University, 169, Changle West Road, Xi'an, Shaanxi, 710038, China.
Zhaoyong
Z
Yan
State Key Laboratory of Cancer Biology, Experimental Teaching Center of Basic Medicine, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China.
Jinliang
J
Xing
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.
Jiaze
J
An
Department of Pain Treatment, Tangdu Hospital, Fourth Military Medical University, 169, Changle West Road, Xi'an, Shaanxi, 710038, China. Electronic address: zhhxtdjr@163.com.
Hongxin
H
Zhang
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D002681:China / Q000453:epidemiology; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D005956:Glucose-6-Phosphate Isomerase / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000235:genetics; D000509:alpha-Fetoproteins / Q000032:analysis
D005819:Genetic Markers; D012333:RNA, Messenger; D000509:alpha-Fetoproteins; D005956:Glucose-6-Phosphate Isomerase