A functional polymorphism of SSBP1 gene predicts prognosis and response to chemotherapy in resected gastric cancer patients
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Qiuchen Li1,*, Falin Qu2,*, Renli Li3, Xianli He2, Yulong Zhai2, Weigang Chen1 and Yong Zheng1
1Department of Gastroenterology, First Affiliated Hospital of the Medical College, Shihezi University, Shihezi, Xinjiang, 832008, China
2Department of General Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi’an, Shaanxi, 710038, China
3Department of General Surgery, The Fourth Hospital of Chinese PLA, Xining, Qinhai, 810007, China
*These authors contributed equally to this work
Yong Zheng, email: firstname.lastname@example.org
Weigang Chen, email: email@example.com
Keywords: single nucleotide polymorphism; gastric cancer; prognosis; single-strand DNA-binding protein 1; chemotherapy
Received: July 27, 2017 Accepted: November 03, 2017 Published: December 02, 2017
Growing evidence has indicated that single-stranded DNA-binding proteins 1 (SSBP1) is involved in tumor initiation and progression. However, effects of single nucleotide polymorphisms (SNPs) in SSBP1 gene on gastric cancer (GC) prognosis are still unknown. In present study, two functional SNPs from SSBP1 were selected and genotyped in a large cohorts of 1030 resected GC patients (326 in the training set, 704 in the validation set) to explore the association of SNPs with patients’ survival. The rs6976500 G allele (CG/GG) genotypes were found significantly associated with both worse overall survival (OS) and recurrence-free survival (RFS) in the training and the independent validation set when compared to C allele genotype, which reaching a more robust statistical significance in the pooled analysis. Furthermore, integration of rs6976500 genotypes and TNM stage significantly improved the prognosis prediction models based on TNM stage alone. In addition, only carriers with at least one G allele of rs6976500 gained significant survival benefit from FOLFOX-based ACT. Mechanistically, SNP rs6976500 G allele genotype could significantly decrease promoter transcriptional activity and markedly reduce expression level of SSBP1 compared with the C allele genotype in GC cells. This was further substantiated by immunohistochemical assay in 70 GC tissue samples. Our study presents the first evidence that SNP rs6976500 G allele genotypes might contribute to GC prognosis by attenuating SSBP1 promoter activity and gene expression, and provides the guidance in refining therapeutic decisions of GC patients. Further exploration on its function is needed to clarify the exact biological mechanism behind.
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