title: Genetic variants in de novo lipogenic pathway genes predict the prognosis of surgically-treated hepatocellular carcinoma.
abstract: Over-expression of de novo lipogenesis (DNL) pathway genes is associated with the prognosis of various types of cancers. However, effects of single nucleotide polymorphisms (SNPs) in these genes on recurrence and death of hepatocellular carcinoma (HCC) patients after surgery are still unknown. A total of 492 primary HCC patients treated with surgery were included in this study. Nine SNPs in 3 genes (ACACA, FASN and ACLY) of DNL pathway were genotyped. Multivariate Cox proportional hazard regression model and Kaplan-Meier curve were used to analyze the association of SNPs with clinical outcomes. Two SNPs in ACACA gene were significantly associated with overall survival of HCC patients. Patients carrying homozygous variant genotype (VV) in rs7211875 had significantly increased risk of death, while patients carrying VV genotype in rs11871275 had significant decreased risk of death, when compared with those carrying homozygous wild-type or heterozygous genotypes. Moreover, patients carrying VV genotype in rs11871275 had decreased recurrence risk, while patients carrying variant genotype in rs4485435 of FASN gene had increased recurrence risk. Further cumulative effect analysis showed significant dose-dependent effects of unfavorable SNPs on both death and recurrence. SNPs in DNL genes may serve as independent prognostic markers for HCC patients after surgery.
authors.affiliation: Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Hequn
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Jingyao
authors.initials: J
authors.lastname: Dai
authors.affiliation: State Key Laboratory of Cancer Biology and Experimental Teaching Center of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Cancer Biology and Experimental Teaching Center of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Yibing
authors.initials: Y
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Cancer Biology and Experimental Teaching Center of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Qu
authors.affiliation: State Key Laboratory of Cancer Biology and Experimental Teaching Center of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Jibin
authors.initials: J
authors.lastname: Li
authors.affiliation: Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Yi
authors.affiliation: Department of Interventional Radiology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, China.
authors.forename: Yefa
authors.initials: Y
authors.lastname: Yang
authors.affiliation: College of Life Science, Northwest University, Xi'an, 710069, China.
authors.forename: Kejing
authors.initials: K
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Cancer Biology and Experimental Teaching Center of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Qichao
authors.initials: Q
authors.lastname: Huang
mesh_terms: D000103:Acetyl-CoA Carboxylase / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000401:mortality* / Q000601:surgery; D054890:Fatty Acid Synthase, Type I / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D050155:Lipogenesis / Q000235:genetics*; D008113:Liver Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000401:mortality* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016896:Treatment Outcome; D047368:Tumor Burden; D055815:Young Adult
chemical_list: C518729:FASN protein, human; D054890:Fatty Acid Synthase, Type I; C000588423:ACACA protein, human; D000103:Acetyl-CoA Carboxylase
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