Genetic variations in genes of metabolic enzymes predict postoperational prognosis of patients with colorectal cancer

Molecular Cancer

Research

Shukui Wang¹  Xianli He²  Guanglong Dong³  Shaogui Wan⁴  Jinliang Xing⁵  Yibing Chen⁵  Haiyan Cao⁵  Jiaojiao Wang⁵  Xiaonan Liu⁶ 

[1] Central Laboratory, Nanjing First Hospital, Nanjing Medical University, 210006, Nanjing, China;Department of General Surgery, Tangdu Hospital, Fourth Military Medical University, 710032, Xi’an, China;Department of General Surgery, The General Hospital of PLA, 100853, Beijing, China;Institute of Pharmacy, Pharmaceutical College of Henan University, 85 Minglun Street, 475001, Kaifeng, Henan, China;State Key Laboratory of Cancer Biology, Experimental Teaching Center of Basic Medicine, Fourth Military Medical University, 169 Changle West Road, 710032, Xi’an, Shaanxi, China;Xijing Hospital of Digestive Disease, Fourth Military Medical University, 710032, Xi’an, China;

关键词: Colorectal cancer;    Prognosis;    Single nucleotide polymorphism;    Succinate dehydrogenase;    Tricarboxylic acid cycle;   

DOI  :  10.1186/s12943-015-0442-x

 received in 2015-04-13, accepted in 2015-09-03,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundGenetic alterations in tricarboxylic acid (TCA) cycle metabolic enzymes were recently linked to various cancers. However, the associations of single nucleotide polymorphisms (SNPs) in genes of these enzymes have not been well studied.MethodsWe genotyped 16 SNPs from 7 genes encoding TCA cycle metabolic enzymes in 697 colorectal carcinoma (CRC) patients receiving surgical resection and analyzed their associations with clinical outcomes by multivariate Cox proportional hazard model. Then, the significant results were validated in another cohort of 256 CRC patients.ResultsWe identified 4 SNPs in 2 genes had significant associations with CRC death risk and 5 SNPs in 3 genes had significant associations with CRC recurrence risk. Similar significant results were confirmed for rs4131826 in SDHC gene, rs544184 in SDHD gene and rs12071124 in FH gene in a validation cohort. Further analysis indicated that unfavorable genotypes exhibited a significant cumulative effect on overall and recurrence-free survival in a dose-dependent manner. Moreover, survival tree analysis indicated that SNP rs4131826 in SDHC gene and SNP rs12071124 in FH gene were the primary factors contributing to the different overall survival time and recurrence-free survival time of CRC patients, respectively. Immunohistochemical analysis further validated the effect of rs4131826 and rs544184 on expression of SDHC and SDHD in tissue samples.ConclusionsOur study suggests that SNPs in TCA cycle metabolic enzymes might be significantly associated with clinical outcomes in Chinese population diagnosed with CRC. Further functional and validated studies are warranted to expend our results to clinical utility.

【 授权许可】

CC BY   
© Dong et al. 2015