| Gastric cancer(GC)is one of the most common malignancies in the world with around 1,221,000 new cases and 865,000 deaths,making it the fifth most frequently diagnosed cancer and the third leading cause of cancer death according to The Journal of the American Medical Association in 2017.Although a steady decline in morbidity and mortality of GC have been observed in developed countries,but the disease burden remains heavy in China.There were 562,000 new cases and 242,000 deaths in China.And the morbidity and mortality of gastric cancer were estimated to be ranked2 nd and 3rd independently in 2018 which have been a serious public health problem globally.Although the response to treatment in a subset of GC patients was improved with the development of chemotherapy and targeted therapy,the 5-year overall survival(OS)rate of gastric cancer still remains 35.9% since without obvious symptom and miss the best time of treatment.A growing number of studies also show that genetic factors played a crucial role on the prognosis of gastric cancer.Different patients histologically diagnosed with the same stage and treated with the same surgery and post-chemotherapy have significantly difference in the prognosis of GC.Toll-like receptors(TLRs),key proteins in innate immunity,appear to contribute to the inflammatory environment in carcinogenesis,including GC.Objective: Toll-like receptors(TLRs)mediate the recognition of Helicobacter pylori(H.pylori)and initiate the innate immune response to infection.Genetic polymorphisms of TLRs play important roles in gastric carcinogenesis and development.The aim of this study was to determine the relationship between single nucleotide polymorphisms(SNPs)in TLR genes in the prognosis of gastric cancer(GC)in order to achieve well-targeted treatment of GC.Methods: From 2008 to 2013 a total of 756 GC patients who underwent tumor resection with negative surgical margin and no distant metastases were included inthis study.The follow-up of the patients was conducted after the surgery at 3 months,6 months,1 year and every 1 year thereafter until the death of the patients or lost to follow-up.Nine SNPs(TLR2: rs3804100,rs7696323,and rs10116253;TLR4:rs10983755,rs11536878,rs1927914,and rs7873784;TLR5: rs5744174;and TLR9:rs187084)in TLR genes were genotyped by MassARRAY assay.Kaplan-Meier survival plots and Cox regression were employed to conduct the associations between SNPs in TLRs and the survival of GC.Then we determined the relationship between different SNPs of TLRs and helicobacter pylori(H.pylori)infection status,and analyzed the relationship between various SNPs of TLRs and the protein expression of TLR2 in GC patients with IHC method.Result: Subjects were excluded if they were lost to follow-up at the first phone interview or died due to complications of the surgery within 30 days after surgery.Finally,a total of 728 subjects were included in the survival analyses.The median follow-up time was 69.5 months,and the 5-year overall survival(OS)rate of GC was49.3%.Multivariate Cox regression indicated that patients with the TLR2 rs3804100 TT genotype exhibited worse survival than those with the CC+CT genotype after adjusting for age,gender,tumor size,histological grade,neural invasion,vascular invasion,depth of invasion,lymph metastasis,chemotherapy,and WHO classification(HR=1.262,95% CI: 1.006-1.582).No significant association was observed between other SNPs and the expression of TLR2 and the prognosis of GC(P >0.05).No synergistic effect was found between TLR2 rs3804100 and H.pylori infection in the prognosis of GC(P = 0.369).There was no TLR2 gene SNPs were found to be associated with TLR2 protein expression(P >0.05).Conclusion: The TLR2 rs3804100 gene polymorphism may be an independent predictor of GC prognosis.There was no synergistic effect between TLRs gene SNPs and H.pylori infection in the prognosis of gastric cancer,and TLR2 gene SNPs were not related to TLR2 protein expression. |
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