Abstract
BackgroundPrevious studies have demonstrated that ATP citrate lyase (ACLY) plays an important role in the development of many cancers. Our current study aims to assess the effects of functional single nucleotide polymorphisms (SNPs) in ACLY gene on recurrence and survival of colorectal cancer (CRC) patients.MethodsA total of 697 resected Chinese CRC patients were included in this study. Two functional single nucleotide polymorphisms in ACLY gene were examined using the Sequenom iPLEX genotyping system. Multivariate Cox proportional hazards model and Kaplan-Meier curve were used for the prognosis analysis.ResultsMultivariate Cox regression analysis showed that there was no significant association between SNPs in ACLY gene and the prognosis of total patient cohort. However, in patients with stage III + IV diseases, the two functional SNPs (rs2304497 and rs9912300) exhibited a significant association with the risks of death (HR = 0.47, 95% CI = 0.24–0.90 and HR = 0.59, 95% CI = 0.37–0.92, respectively) and recurrence (HR = 0.46, 95% CI = 0.24–0.86 and HR = 0.54, CI = 0.35–0.83, respectively). Kaplan-Meier analysis indicated that those CRC patients carrying heterozygous (WV) or homozygous variant (VV) genotypes in rs2304497 and rs9912300 had significantly better overall survival (OS) and recurrence-free survival (RFS). Moreover, we observed remarkable cumulative effects of these two SNPs on overall survival and recurrence-free survival (P for trend = 0.012 and 0.003, respectively). Compared with patients carrying zero unfavorable genotype, those carrying two unfavorable genotypes had a 2.24-fold and 2.33-fold increase of death and recurrence risks, respectively.ConclusionsThe SNPs in ACLY gene may serve as independent prognostic markers for patients with advanced stage CRC.Electronic supplementary materialThe online version of this article (doi:10.1186/s12957-015-0440-x) contains supplementary material, which is available to authorized users.
Highlights
Previous studies have demonstrated that ATP citrate lyase (ACLY) plays an important role in the development of many cancers
A total of 697 colorectal cancer (CRC) patients were included in this study, with a median age of 60 years
We found that in patients with advanced stage tumor, the heterozygous variant (WV) and homozygous variant (VV) genotypes in both rs2304497 and rs9912300 reduced the death risk of CRC in the dominant model (HR = 0.47, 95% confidence interval (CI) = 0.24–0.90 and hazard ratio (HR) = 0.59, 95% confidence interval (95% CI) = 0.37–0.92, respectively)
Summary
Previous studies have demonstrated that ATP citrate lyase (ACLY) plays an important role in the development of many cancers. Fatty acids play an important role in a variety of cellular processes. De novo lipogenesis (DNL) is an endogenous pathway whereby carbohydrates are converted to fatty acids [1]. Migita et al have reported that the overexpression of ACLY is wellcorrelated with stage, differentiation grade, and a poorer prognosis in non-small cell lung cancer [4]. All these data strongly support the idea that the ACLY is involved in the development and progression of human cancers
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