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Polymorphisms in Genes of the De Novo Lipogenesis Pathway and Overall Survival of Hepatocellular Carcinoma Patients Undergoing Transarterial Chemoembolization

  • Wu, You-Sheng (State Key Laboratory of Cancer Biology, Experimental Teaching Center of Basic Medicine, Fourth Military Medical University) ;
  • Bao, Deng-Ke (State Key Laboratory of Cancer Biology, Experimental Teaching Center of Basic Medicine, Fourth Military Medical University) ;
  • Dai, Jing-Yao (Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University) ;
  • Chen, Cheng (State Key Laboratory of Cancer Biology, Experimental Teaching Center of Basic Medicine, Fourth Military Medical University) ;
  • Zhang, Hong-Xin (Department of Pain treatment, Tangdu Hospital, Fourth Military Medical University) ;
  • Yang, YeFa (Department of Interventional Radiology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University) ;
  • Xing, Jin-Liang (State Key Laboratory of Cancer Biology, Experimental Teaching Center of Basic Medicine, Fourth Military Medical University) ;
  • Huang, Xiao-Jun (State Key Laboratory of Cancer Biology, Experimental Teaching Center of Basic Medicine, Fourth Military Medical University) ;
  • Wan, Shao-Gui (Institute of Pharmacy, Pharmaceutical College of Henan University)
  • Published : 2015.03.04

Abstract

Aberrant expression of genes in de novo lipogenesis (DNL) pathway were associated with various cancers, including hepatocellular carcinoma (HCC). Single nucleotide polymorphisms (SNPs) of DNL genes have been reported to be associated with prognosis of some malignancies. However, the effects of SNPs in DNL genes on overall survival of HCC patients receiving transarterial chemoembolization (TACE) treatment are still unknown. In present study, nine SNPs in three genes (ACLY, ACACA and FASN) in DNL pathway were genotyped using the Sequenom iPLEX genotyping system in a hospital-based cohort with 419 HCC patients treated with TACE, and their associations with HCC overall survival were evaluated by Cox proportional hazard regression analysis under three genetic models (additive, dominant and recessive). Although we did not find any significant results in total analysis (all p>0.05), our stratified data showed that SNP rs9912300 in ACLY gene was significantly associated with overall survival of HCC patients with lower AFP level and SNP rs11871275 in ACACA gene was significantly associated with overall survival of HCC patients with higher AFP level. We further identified the significant interactions between AFP level and SNP rs9912300 or rs11871275 in the joint analysis. Conclusively, our data suggest that genetic variations in genes of DNL pathway may be a potential biomarker for predicting clinical outcome of HCC patients treated with TACE.

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