Abstract
Abstract Abstract:Aim:Variant in pri-miRNA could affect miRNA expression and mature process or splicing efficiency, thus altering the hereditary susceptibility and prognosis of cancer. We aimed to assess miRNA-let-7 single nucleotide polymorphisms (SNP) associated with the risk and prognosis of gastric cancer (GC) as predicting biomarkers, and furthermore, its possible mechanisms. Method:We designed a two-stage case-control study to screen four miRNA SNPs (pri-let-7a-2 rs629367 and rs1143770, pri-let-7a-1 rs10739971, pri-let-7f-2 rs17276588) in 107 GC patients, 107 atrophic gastritis (AG), and matched 124 controls using PCR-RFLP. Two promising SNPs (pri-let-7a-2 rs629367 and pri-let-7a-1 rs10739971) were validated in another independent 1949 samples (including 579 GC patients, 649 AG and 721 controls) using Sequenom MassARRAY platform and sequencing. Results: We found that pri-let-7a-2 rs629367 CC variant genotype was associated with increased risks of GC and AG by 1.83-fold and 1.86-fold, respectively. For GC prognosis, patients with rs629367 CC genotype had significantly poorer survival than patients with AA genotype (log-rank P=0.004). We further investigated the let-7a expression levels in serum and found that let-7a expression elevated gradually for rs629367 AA, CA, CC genotype in the AG group (P=0.043). Furthermore, we confirmed these findings in vitro study by overexpressing let-7a carrying pri-let-7a-2 wild-type A or polymorphic-type C allele (P<0.001). Conclusion: pri-let-7a-2 rs629367 CC genotype could increase the risks of GC as well as AG and was also associated with poor survival of GC, which possibly by affecting the mature let-7a expression, and could serve as a predicting biomarker for high-risk and poor prognosis of GC. Note: This abstract was not presented at the meeting. Citation Format: Qian Xu, Yuan Yuan. Pri-let-7a-2 rs629367 associated with increased risk and poor survival of gastric cancer in Chinese by up-regulated let-7a expression. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1489. doi:10.1158/1538-7445.AM2014-1489
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