Single nucleotide polymorphism rs13042395 in the SLC52A3 gene as a biomarker for regional lymph node metastasis and relapse-free survival of esophageal squamous cell carcinoma patients

BMC Cancer

Research Article

Shan-Shan Li¹  En-Min Li¹  Jian-Yi Wu¹  Hua-Zhen Tan¹  Lin Long¹  Ji-Wei Jiao¹  Wei Wang¹  Yi-Wei Xu²  Yu-Hui Peng³  Zhi-Yong Wu⁴  Jian-Jun Zhang⁵  Li-Yan Xu⁶ 

[1] Key Laboratory of Molecular Biology in High Cancer Incidence Coastal Chaoshan Area of Guangdong Higher Education Institutes, Shantou University Medical College, No. 22, Xinling Road, 515041, Shantou, China;Department of Biochemistry and Molecular Biology, Shantou University Medical College, No. 22, Xinling Road, 515041, Shantou, China;Key Laboratory of Molecular Biology in High Cancer Incidence Coastal Chaoshan Area of Guangdong Higher Education Institutes, Shantou University Medical College, No. 22, Xinling Road, 515041, Shantou, China;Department of Biochemistry and Molecular Biology, Shantou University Medical College, No. 22, Xinling Road, 515041, Shantou, China;Department of Clinical Laboratory, Cancer Hospital of Shantou University Medical College, No.7, Raoping Road, 515041, Shantou, Guangdong, China;Key Laboratory of Molecular Biology in High Cancer Incidence Coastal Chaoshan Area of Guangdong Higher Education Institutes, Shantou University Medical College, No. 22, Xinling Road, 515041, Shantou, China;Department of Clinical Laboratory, Cancer Hospital of Shantou University Medical College, No.7, Raoping Road, 515041, Shantou, Guangdong, China;Key Laboratory of Molecular Biology in High Cancer Incidence Coastal Chaoshan Area of Guangdong Higher Education Institutes, Shantou University Medical College, No. 22, Xinling Road, 515041, Shantou, China;Department of Oncologic Surgery, Shantou Central Hospital, Affiliated Shantou Hospital of Sun Yat-Sen University, 515041, Shantou, China;Key Laboratory of Molecular Biology in High Cancer Incidence Coastal Chaoshan Area of Guangdong Higher Education Institutes, Shantou University Medical College, No. 22, Xinling Road, 515041, Shantou, China;Department of Preventive Medicine, Shantou University Medical College, No. 22, Xinling Road, 515041, Shantou, China;Key Laboratory of Molecular Biology in High Cancer Incidence Coastal Chaoshan Area of Guangdong Higher Education Institutes, Shantou University Medical College, No. 22, Xinling Road, 515041, Shantou, China;Institute of Oncologic Pathology, Shantou University Medical College, No. 22, Xinling Road, 515041, Shantou, China;

关键词: Esophageal squamous cell carcinoma;    Single nucleotide polymorphism;    SLC52A3;    Tumor characteristics;    Relapse-free survival;   

DOI  :  10.1186/s12885-016-2588-3

 received in 2015-08-12, accepted in 2016-06-23,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundSLC52A3 was recently identified as a susceptibility gene for esophageal squamous cell carcinoma (ESCC). However, associations between the single nucleotide polymorphisms (SNPs) rs13042395 (C > T) and rs3746803 (G > A) in SLC52A3 and risk, tumor characteristics and survival of ESCC patients remain inconclusive and of unknown prognostic significance.MethodsAnalyses of the association between SNPs in SLC52A3 and ESCC risk were performed on 479 ESCC cases, together with 479 controls, in a case-control study. Blood samples for cases and controls were collected and genotyped by real-time polymerase chain reaction (PCR) using TaqMan assays. Among the 479 ESCC cases, 343 cases with complete clinical data were used to investigate the association between SNPs and ESCC clinical characteristics; 288 cases with complete clinical data and 5-year follow-up data were used to analyze the association between SNPs and prognosis. Dual luciferase reporter assays and electrophoretic mobility shift assays (EMSAs) were used to investigate the biological function of rs13042395.ResultsNo association was found between SLC52A3 rs3746803 and susceptibility, tumor characteristics or survival of ESCC patients. For rs13042395, TT genotype carriers were likely to have reduced lymph node metastasis (odds ratio (OR) = 0.55, 95 % confidence interval (CI), 0.31–0.98) and longer relapse-free survival time (P = 0.03) . Also, both rs13042395 (hazard ratio (HR) = 0.62, 95 % CI, 0.38–0.99) and regional lymph node metastasis (HR = 2.06, 95 % CI, 1.36–3.13 for N1 vs. N0; HR = 2.88, 95 % CI, 1.70–4.86 for N2 vs. N0; HR = 2.08, 95 % CI, 1.01–4.30 for N3 vs. N0) were independent factors affecting relapse-free survival for ESCC patients who underwent surgery. Dual luciferase reporter assays and EMSAs suggested that the CC genotype of rs13042395 enhanced SLC52A3 expression, probably via binding with specific transcription factors.ConclusionsThe rs13042395 polymorphism in SLC52A3 is associated with regional lymph node metastasis and relapse-free survival in ESCC patients.

【 授权许可】

CC BY   
© The Author(s). 2016