溶质载体转运蛋白22A3基因rs7758229多态性与胰腺癌预后的关系

Correlation between solute carrier transporter 22A3 gene rs7758229 polymorphism and prognosis of pancreatic cancer

目的探讨溶质载体转运蛋白22A3(SLC22A3)基因rs7758229位点多态性与胰腺癌预后相关性。方法选取2014年3月30日至2016年3月30日宁夏医科大学总医院收治的100例接受手术治疗的可切除胰腺癌患者,年龄范围为35~79岁,年龄(49.1±5.7)岁;男61例,女39例;胰头颈癌66例,胰体尾癌34例,TNM分期参考第7版美国癌症联合委员会(AJCC)胰腺癌分期系统,其中Ⅰ期19例、Ⅱ期56例、Ⅲ期25例,于入院第2天抽取空腹静脉血5 ml,使用测序法检测SLC22A3基因rs7758229位点多态性。对患者进行随访,终点为全因死亡,观察rs7758229位点多态性与胰腺癌预后相关性。:应用SPSS 25.0统计软件分析,Hardy Weinberg平衡被用于检测患者基因型分布偏离情况,使用χ^2检验分析SLC22A3基因rs7758229位点多态性患者临床资料相关性,使用Kaplan-Meier法比较SLC22A3基因rs7758229位点多态性与OS相关性;使用Cox比例风险模型对影响OS的预后因素分析。结果基因型分析结果表明SLC22A3基因rs7758229位点3种基因型(GG型、GT型、TT型)在胰腺癌的分布频率不同,其中GG型28例(28.0%);GT型51例(51.0%);TT型21例(21.0%)。rs7758229单核甘酸多态性与肿瘤分化程度、临床分期间差异有统计学意义(χ^2=10.209、10.826,P<0.05)。失访6例(GG型2例,GT型3例,TT型1例),中位随访时间为46个月,死亡73例。Kaplan-Meier分析并Log-rank检验显示,比较rs7758229 GG型患者,rs7758229 TT型患者总生存期(OS)缩短(Log-rank:χ^2=11.254,P<0.05),差异有统计学意义。Cox比例风险模型结果显示,rs7758229单核甘酸多态性[TT型比GG型,P<0.05,比值比(OR):2.357,95%可信区间(CI):1.524~6.317]、TNM分期(P<0.05,OR:1.194,95%CI:0.031~3.491)、年龄(P<0.05,OR:1.354,95%CI:1.067~4.357)、肿瘤分化程度(P<0.05,OR:1.687,95%CI:1.108~4.217)、切缘情况(P<0.05,OR:1.947,95%CI:1.354~5.218)是影响胰腺癌患者OS的独立预后因素。结论SLC22A3基因rs7758229位点多态性与胰腺癌生存率相关,TT型患者的OS更短。

Objective To investigate the relationship between solute carrier transporter 22A3(SLC22A3)gene rs7758229 polymorphism and prognosis of pancreatic cancer.Methods One hundred patients with resectable pancreatic cancer who underwent surgery were admitted to our hospital from March 30,2014 to March 30,2016 were selected.There were were 61 male and 39 female patients,aging from 35 to 79 years with a median age of(49.1±5.7)years.The location included head and neck of the pancreas(n=66),body and tail of pancreas(n=34).According to the 7th American Joint Committee on Cancer(AJCC)Pancreatic Cancer Staging System,19 cases were in stage I,56 cases were in stageⅡand 25 cases in stageⅢ.On the 2nd day after admission,5 ml of fasting venous blood was taken,and the polymorphism of SLC22A3 gene rs7758229 was detected by DNA extraction kit and sequencing method.The patients were followed up and the end point was all-cause death.The correlation between polymorphism of rs7758229 and the prognosis of pancreatic cancer,and the factors affecting the overall survival(OS)of the patients were analyzed.The date analysis was conducted by SPSS 25.0;the gene type distribution deviation was tested by Hardy-Weinberg equilibrium,the correlation analysis of clinical date was analyzed byχ^2 test analysis.The correlation between polymorphism of rs7758229 and the prognosis of pancreatic cancer,and the factors affecting the OS of the patients were analyzed by by Kaplan-Meier method and Cox model respectively.Results There were 28 cases(28.0%)of GG type,51 cases(51.0%)of GT type,and 21 cases(21.0%)of TT type.The rs7758229 mononucleic acid polymorphism was significantly correlated with the degree of tumor differentiation and clinical stage(χ^2=10.209,10.826,P<0.05).Six patients were lost to follow-up(2 patients with GG,3 patients with GT,and 1 patient with TT)with a median follow-up of 46 months.There were 73 deaths.Kaplan-Meier analysis and Log-rank test showed that overall survival(OS)was significantly shortened in patients with rs7758229 TT as compared with that in those with rs7758229 GG(Log-rank:χ^2=11.254,P<0.05).Cox proportional hazard model results showed that rs7758229 mononuclear acid polymorphism[TT type/GG type,P<0.05,odds ratio(OR):2.357,95%confidence interval(CI):1.524-6.317],TNM stage(P<0.05,OR:1.194,95%CI:0.031-3.491),age(P<0.05,OR:1.354,95%CI:1.067-4.357),degree of tumor differentiation(P<0.05,OR:1.687,95%CI:1.108-4.217),and margin situation(P<0.05,OR:1.947,95%CI:1.354-5.218)were independent prognostic factors influencing OS in patients with pancreatic cancer(P<0.05).Conclusion The rs7758229 polymorphism of SLC22A3 gene is associated with the survival rate of pancreatic cancer.The OS of TT patients is shorter.