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Genetic variations in IDH gene as prognosis predictors in TACE-treated hepatocellular carcinoma patients

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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.

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Acknowledgements

This work was supported by National Natural Science Foundation of China (No. 81302054, No. 81272522 and No. 81270505) and grants2011gr0239 from the International S & T Cooperation Program of China.

Conflict of interest

None declared.

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Authors and Affiliations

  1. Department of Pain Treatment, Tangdu Hospital, Fourth Military Medical University, 1 Xinsi Road, Xi’an, 710038, China

    Huiqing Zhang & Hongxin Zhang

  2. Experimental Teaching Center of Basic Medicine, Fourth Military Medical University, Xi’an, China

    Xu Guo & Yousheng Wu

  3. Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, 710032, China

    Jingyao Dai

  4. Department of Interventional Radiology, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China

    Naijian Ge & Yefa Yang

  5. Department of Interventional Radiology, Zhejiang University Lishui Hospital and Lishui Center Hospital, Lishui, 323000, China

    Jiansong Ji

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  1. Huiqing Zhang
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Correspondence to Jiansong Ji or Hongxin Zhang.

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Huiqing Zhang and Xu Guo have contributed equally to this work.

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Zhang, H., Guo, X., Dai, J. et al. Genetic variations in IDH gene as prognosis predictors in TACE-treated hepatocellular carcinoma patients. Med Oncol 31, 278 (2014). https://doi.org/10.1007/s12032-014-0278-z

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  • DOI: https://doi.org/10.1007/s12032-014-0278-z

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