微卫星不稳定性和PTEN突变对可切除胃癌辅助化疗疗效和预后预测的临床观察  

Clinical observation of microsatellite instability and PTEN mutations in predicting the efficacy and prognosis of adjuvant chemotherapy for resectable gastric cancer

作　　者：蒋志斌 李伟 王顺 刘广超 JIANG Zhibin;LI Wei;WANG Shun;LIU Guangchao(The Second Department of General Surgery,980 Hospital,Joint Logistic Support Force,PLA,Shijiazhuang 054300,China)

机构地区：[1]解放军联勤保障部队第九八〇医院普外二科,石家庄054300

出　　处：《临床肿瘤学杂志》2024年第6期545-550,共6页Chinese Clinical Oncology

摘　　要：目的检测胃癌组织中微卫星不稳定性(MSI)与磷酸酶和紧张素同源物(PTEN)基因突变情况,及其与胃癌患者辅助化疗疗效和预后的关系。方法收集解放军联勤保障部队第九八〇医院2021年1月至2022年6月间接受R_(0)D_(2)胃切除术Ⅱ/Ⅲ期患者115例,采用免疫组化法检测PTEN蛋白和程序性死亡受体配体1(PD-L1)蛋白表达,采用二代测序(NGS)分析PTEN拷贝数变化。采用多重聚合酶链式反应(PCR)检测MSI状态。Kaplan-Meier法绘制生存曲线,生存差异行Log-rank检验。Cox比例风险回归模型分析影响胃癌患者预后的因素。结果共23例PTEN突变,55例PTEN蛋白阴性表达。PTEN突变与PTEN蛋白表达、PD-L1表达、EBV感染及MSI状态有关,差异具有统计学意义(P<0.05)。根据MSI状态和PTEN突变,将患者分为MSS/PTEN wild亚组(n=83)、MSI/PTEN wild亚组(n=9)、MSI/PTEN mutant亚组(n=12)和MSS/PTEN mutant亚组(n=11),四组中位OS分别为16.50个月、18.20个月、7.36个月和4.50个月,差异有统计学意义(P<0.001)。多因素Cox风险比例回归模型分析显示,PD-L1表达和MSI/PTEN状态是影响胃癌患者OS的独立因素(P<0.05)。在MSS/PTEN mutant亚组中,PD-L1阴性患者OS较PD-L1阳性患者预后差(P=0.035)。在MSI/PTEN wild亚组或MSS/PTEN wild亚组,PD-L1表达和预后无关(P>0.05)。PD-L1表达是MSS/PTEN mutant亚组OS的独立因素(HR=0.612,95%CI:0.389~0.962,P=0.033)。结论分子分型与PD-L1表达相结合可作为一种潜在的策略更好地预测胃癌患者的预后。Objective To detect microsatellite instability(MSI)and phosphatase and tensin homolog(PTEN)gene mutations in gastric cancer tissue,and their relationship with the efficacy and prognosis of adjuvant chemotherapy in gastric cancer patients.Methods A total of 115 patients with stageⅡ/Ⅲindirect R_(0)D_(2) gastrectomy at the 980 Hospital of the Joint Logistics Support Force of the People's Liberation Army from January 2021 to June 2022 were collected.The expression of PTEN protein and programmed death receptor ligand 1(PD-L1)protein was detected using immunohistochemistry,and changes in PTEN copy number were analyzed using second-generation sequencing(NGS).Multiple polymerase chain reaction(PCR)was used to detect MSI status.Kaplan-Meier method was used to plot survival curves,and log rank tests were performed on survival differences.Cox proportional hazards regression model analysis of factors affecting the prognosis of gastric cancer patients.Results There were a total of 23 PTEN mutations and 55 PTEN protein negative expressions.PTEN mutations are related to PTEN protein expression,PD-L1 expression,EBV infection,and MSI status,and the differences are statistically significant(P<0.05).According to MSI status and PTEN mutations,patients were divided into MSS/PTEN wild subgroup(n=83),MSI/PTEN wild subgroup(n=9),MSI/PTEN mutant subgroup(n=12),and MSS/PTEN mutant subgroup(n=11).The median OS of the four groups were 16.50,18.20,7.36 and 4.50 months,respectively,with statistically significant differences(P<0.001).Multivariate Cox risk proportional regression model analysis showed that PD-L1 expression and MSI/PTEN status were independent factors affecting OS in gastric cancer patients(P<0.05).In the MSS/PTEN mutant subgroup,PD-L1 negative patients had a poorer prognosis in OS compared to PD-L1 positive patients(P=0.035).In the MSI/PTEN wild subgroup or MSS/PTEN wild subgroup,PD-L1 expression was not associated with prognosis(P>0.05).PD-L1 expression is an independent factor for OS in the MSS/PTEN mutant subgroup(HR=0.6

关 键 词：胃癌 磷酸酶和紧张素同源物 微卫星不稳定性 预后 EPSTEIN-BARR病毒 

分 类 号：R735.2[医药卫生—肿瘤]