Abstract
Objective: TNFAIP2 is a novel gene induced by TNF-α and participates in inflammatory reaction and tumor angiogenesis. This study aims to understand the correlation between TNFAIP2 gene polymorphism and prediction as well as prognosis of gastric cancer (GC) in a Chinese population.Methods: One thousand two hundred seventy-nine cases were enrolled, including 640 GC and 639 non-cancer cases. The functional tagSNPs of the TNFAIP2 gene were screened by Haploview software and NIH Snpinfo website. Human whole-blood genomic DNA was extracted by phenol chloroform method and analyzed by KASP SNP typing and sequencing method. ELISA was used to determine the expression of TNFAIP2 protein in serum samples. The miRNAs bound to TNFAIP2 3′ UTR rs8126 were predicted by MirSNP and TargetScan database. SPSS 22.0 software was used for statistical analysis, and P < 0.05 showed statistical difference.Results: Four functional TNFAIP2 tagSNPs were found by bioinformatics analysis. TNFAIP2 rs8126 T>C polymorphism increased GC risk, and the risk in TC genotype cases was higher than that in TT genotype cases (P = 0.001, OR = 1.557). In the dominant model, the TNFAIP2 rs8126 polymorphic carrier was 1.419 times higher (P = 0.007). TNFAIP2 rs710100 C>T polymorphism, TNFAIP2 rs3759571 G>A polymorphism, and TNFAIP2 rs3759573 A>G polymorphism were not correlated with GC risk. In the subgroup analysis, TNFAIP2 rs8126 TC genotype cases had a higher GC risk in male, aged 60 years or older, Helicobacter pylori-negative, non-smoking, and non-drinking. However, there was no correlation between TNFAIP2 SNPs and GC prognosis. The TNFAIP2 protein concentration in GC patients was significantly different from that in healthy persons (P = 0.029), but it was not associated with GC prognosis. The high or low expression of TNFAIP2 protein had no significant difference with gender, age, H. pylori infection, smoking, and drinking in GC patients. The serum TNFAIP2 protein expression in rs8126 TT genotype carriers was significantly higher than that in rs8126 CC genotype carriers (P < 0.001).Conclusion: TNFAIP2 3′ UTR rs8126 T>C polymorphism was associated with GC risk in a Chinese population, especially in cases with males aged 60 years or older, H. pylori negative, non-smoking and non-drinking. Compared with healthy persons, serum TNFAIP2 protein expression was higher in Chinese GC patients, and TNFAIP2 3′ UTR rs8126 T>C polymorphism might affect TNFAIP2 protein expression.
Highlights
Gastric cancer (GC) is considered to be one of the most common malignant tumors in the world [1]
The correlation between Tumor necrosis factor alpha-induced protein 2 (TNFAIP2) 3′ UTR rs8126 T>C polymorphism and TNFAIP2 protein expression was analyzed by different polymorphism genotypes in 103 GC patients, and we found that TNFAIP2 protein expression in rs8126 TT genotype carriers was significantly higher than that in rs8126 CC genotype carriers (P < 0.001) (Table 12)
Studies have found that Single nucleotide polymorphism (SNP) in mRNA 3′ UTR may impact the miRNA-mediated expression and regulation of oncogenes and tumor suppressors and confirmed that TNFAIP2 3′ UTR SNPs are correlated with risk of multiple malignancies, especially that TNFAIP2 3′ UTR rs8126 polymorphism may affect TNFAIP2 expression in GC, SCCHN, and esophageal squamous cell carcinoma (ESCC) by disturbing the binding of miR-184 with TNFAIP2 mRNA [14, 18, 19]
Summary
Gastric cancer (GC) is considered to be one of the most common malignant tumors in the world [1]. It is usually asymptomatic or has mild symptoms in the early days but is prone to recurrence and metastasis due to tumor specificity and heterogeneity [2,3,4]. The studies on gene polymorphism can lay an important foundation of molecular biology for revealing the mechanism of malignant tumors, and they have important roles in clarifying tumor susceptibility and predicting the development trend of tumors. Single nucleotide polymorphism (SNP), as the most common type of human genetic variation, is an important part of the research on gene polymorphism and can be used to explore the mechanism of tumor generation [12, 13]
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