title: Genetic variations in IDH gene as prognosis predictors in TACE-treated hepatocellular carcinoma patients.
abstract: Metabolic reprogramming is an important hallmark of cancer cells, including the alterations of activity and expression in tricarboxylic acid (TCA) cycle key enzymes. Previous studies have reported the associations between tumor formation and three core enzymes involved in the TCA cycle. However, the association between functional single nucleotide polymorphisms (SNPs) in one of TCA cycle key gene isocitrate dehydrogenase (IDH) and the overall survival of hepatocellular carcinoma (HCC) patients treated with transcatheter arterial chemoembolization (TACE) has never been investigated. Five functional SNPs in IDH1 and IDH2 genes were genotyped using the Sequenom iPLEX genotyping system in a cohort of 419 unresectable Chinese HCC patients treated with TACE. Multivariate Cox proportional hazards model and Kaplan-Meier curve were used for the prognosis analysis. We found that SNPs rs12478635 in IDH1 and rs11632348 in IDH2 gene exhibited significant associations with death risk in HCC patients in the dominant model (HR 1.33; 95 % CI 1.02-1.73; P = 0.037) and in recessive model (HR 1.87; 95 % CI 1.27-2.75; P = 0.001), respectively. Moreover, we observed a cumulative effect of these two SNPs on HCC overall survival, indicating a significant trend of death risk increase with increasing number of unfavorable genotypes (P for trend = 0.001). Additionally, our data suggest that unfavorable genotypes of two SNPs may be used as an independent prognostic marker in those with advanced stage and patients with serum AFP <200 μg/L. Our results for the first time suggest that IDH gene polymorphisms may serve as an independent prognostic marker for HCC patients treated with TACE.
authors.affiliation: Department of Pain Treatment, Tangdu Hospital, Fourth Military Medical University, 1 Xinsi Road, Xi'an, 710038, China.
authors.forename: Huiqing
authors.initials: H
authors.lastname: Zhang
authors.forename: Xu
authors.initials: X
authors.lastname: Guo
authors.forename: Jingyao
authors.initials: J
authors.lastname: Dai
authors.forename: Yousheng
authors.initials: Y
authors.lastname: Wu
authors.forename: Naijian
authors.initials: N
authors.lastname: Ge
authors.forename: Yefa
authors.initials: Y
authors.lastname: Yang
authors.forename: Jiansong
authors.initials: J
authors.lastname: Ji
authors.forename: Hongxin
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D016461:Chemoembolization, Therapeutic / Q000639:trends; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D008113:Liver Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011237:Predictive Value of Tests; D011379:Prognosis; D015996:Survival Rate / Q000639:trends; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C538784:IDH2 protein, human; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human