Genetic variants in de novo lipogenic pathway genes predict the prognosis of surgically-treated hepatocellular carcinoma.

Hequn Jiang,Qichao Huang,Cheng Yi,Yibing Chen,Jingyao Dai,Xiaojun Huang,Kejing Zhang,Ping Qu,Yefa Yang,Jibin Li

doi:10.1038/srep09536

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.

Highlights

Over-expression of de novo lipogenesis (DNL) pathway genes is associated with the prognosis of various types of cancers
In the present study, we evaluated the effects of 9 Single nucleotide polymorphism (SNP) in three DNL pathway genes (ACACA, fatty-acid synthase (FASN) and ATP citrate lyase (ACLY)) on the prognosis of Chinese hepatocellular carcinoma (HCC) patients with surgical resection
Our data demonstrated that SNPs rs7211875 and rs11871275 in the acetyl-CoA carboxylase alpha (ACACA) gene were significantly associated with the overall survival (OS) of HCC patients, whereas rs11871275 in ACACA gene and rs4485435 in FASN gene were significantly associated with the recurrence-free survival (RFS) of patients

Summary

Introduction

Over-expression of de novo lipogenesis (DNL) pathway genes is associated with the prognosis of various types of cancers. Effects of single nucleotide polymorphisms (SNPs) in these genes on recurrence and death of hepatocellular carcinoma (HCC) patients after surgery are still unknown. The overexpression of FASN or ACACA in tumor tissues has been associated with poor clinical outcomes of prostate, breast, nasopharyngeal, colon, ovarian and lung cancer www.nature.com/scientificreports patients[5,13,14,15,16,17,18]. Quite a few studies have investigated the relationship between single nucleotide polymorphisms (SNPs) of DNL genes and development or prognosis of several tumors such as uterine leiomyomata, breast and prostate cancers[21,22,23,24]. We assessed the effects of nine SNPs in the three key genes of DNL pathway on the prognosis of HCC patients in a cohort of 492 Chinese subjects

Methods

Results

Discussion

Conclusion