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.

Hua-Zhen Tan,Li-Yan Xu,Ji-Wei Jiao,Shan-Shan Li,Wei Wang,Jian-Yi Wu,Zhi-Yong Wu,Lin Long,Yi-Wei Xu,Jian-Jun Zhang,En-Min Li,Yu-Hui Peng

doi:10.1186/s12885-016-2588-3

Abstract

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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2588-3) contains supplementary material, which is available to authorized users.

Highlights

SLC52A3 was recently identified as a susceptibility gene for esophageal squamous cell carcinoma (ESCC)
The rs13042395 polymorphism in SLC52A3 is associated with regional lymph node metastasis and relapse-free survival in ESCC patients
Lack of association between SLC52A3 single nucleotide polymorphisms (SNPs) and ESCC susceptibility The observed genotype frequencies for the two polymorphisms of SLC52A3 in the controls conformed to the Hardy–Weinberg equilibrium (P = 0.06 and 0.80 for rs13042395 and rs3746803, respectively)

Summary

Introduction

SLC52A3 was recently identified as a susceptibility gene for esophageal squamous cell carcinoma (ESCC). According to a Chinese national annual cancer registration report in 2010, esophageal cancer is the fifth most common malignant tumor in China, with an incidence of 21.88/105 [2]. The survival for ESCC patients is poor, with a 5-year overall survival rate below 13.0 % [4, 5]. On one hand, this outcome is partly because of the lack of effective biomarkers for the early detection of ESCC, which results in most ESCC cases presenting at an advanced stage at the time of diagnosis [6]. Effective biomarkers for the early detection and relapse of ESCC are urgently needed

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