TIN2基因突变与胃癌手术患者预后生存的关系分析

The relationship between TIN2 gene mutation and prognosis of patients undergoing gastric cancer surgery

目的分析(TIN2)基因突变与胃癌手术患者预后生存的关系。方法回顾性分析2016年6月至2017年12月重庆市第四人民医院收治的96例胃癌患者临床资料。提取其术后胃癌组织标本、癌旁正常胃黏膜组织标本(96份)中DNA,行PCR扩增后对TIN2基因的6号外显子进行测序,经序列分析找出TIN2基因突变位点,对突变者进行生物学信息分析,并比较TIN2基因突变与未突变患者临床病理资料、2年内生存预后。结果24例(25.00%)胃癌标本发现TIN2基因2个突变点,其中6例TIN2基因6号外显子第90位碱基C/C突变为C/T,18例胃癌TIN2基因6号外显子第241位碱基G/G突变为A/A,胃癌组织TIN2基因突变率高于癌旁正常组织2.08%(2/96)(P<0.05);2个突变点均为错义突变,SNP突变位点预测显示,TIN2基因6号外显子第90位碱基C/C突变为C/T较第241位碱基G/G突变为A/A对TIN2蛋白功能的影响更大;肿瘤直径≥5 cm、分化程度低、TNM分期Ⅲ期的胃癌患者TIN2基因突变率高于肿瘤直径<5 cm、分化程度中高、TNM分期Ⅰ~Ⅱ期者(P<0.05);TIN2基因突变患者1年、2年生存率96.51%、52.77%低于TIN2未突变者100.00%、60.23%,但差异无统计学意义(P>0.05)。结论胃癌患者易发生TIN2基因错义突变,其中6号外显子第90位碱基C/C突变为C/T对蛋白功能影响更大,TIN2基因突变也与胃癌患者病理特征、术后预后生存有一定关系,可能在胃癌发生发展中起着一定作用。

Objective To analyze the relationship between TIN2 and prognosis of patients with gastric cancer surgery.Methods The clinical data of 96 patients with gastric cancer who were admitted to the Fourth People's Hospital of Chongqing from June 2016 and December 2017 were retrospectively analyzed.DNA was extracted from gastric cancer tissue specimens and normal gastric mucosa tissue specimens(96 specimens)adjacent to cancer for PCR amplification.Then,the exon 6 of TIN2 gene was sequenced,and the site with TIN2 gene mutation was found through sequence analysis.The mutants were analyzed for biological information.The clinical and pathological data and 2-year survival of patients with TIN2 gene mutation and those without were compared.Results Two TIN2 gene mutations were found in 24 gastric cancer specimens(25.00%).Among them,the 90th base C/C mutation of TIN2 gene exon 6 had mutated to C/T in 6 specimens,and the 241st base G/G of gastric cancer TIN2 gene exon 6 had mutated to A/A in 18 specimens.The mutation rate of TIN2 gene in gastric cancer tissues was higher than that in normal adjacent tissues 2.08%(2/96)(P<0.05).Both mutations were missense mutations.SNP mutation site prediction showed that the 90th base C/C mutating to C/T in TIN2 gene exon 6 had a greater effect on TIN2 protein function than the 241st base G/G mutating to A/A.There were statistically significant differences in the mutation rate of TIN2 gene between patients with different tumor diameters,different differentiation degrees and different TNM stages(P<0.05).The 1-year and 2-year survival rates of patients with TIN2 gene mutation were lower than those without(96.51%vs.100.00%、52.77%vs.60.23%,P>0.05).Conclusion Patients with gastric cancer are prone to have missense mutations in the TIN2 gene.Besides,the 90th base C/C mutating to C/T in exon 6 has a greater effect on protein function.TIN2 gene mutation is also associated with pathological characteristics and prognosis of gastric cancer.It may play a certain role in the occurrence and development of gastric cancer.