甲基化Septin9基因、循环肿瘤细胞与胃癌根治手术预后的关系

The correlation between peripheral blood methylated Septin9 gene,expression of circulating tumor cells and their subtypes with the efficacy and prognosis of gastric cancer radical resection

目的:探讨外周血中甲基化的Septin9基因(mSEPT9)、循环肿瘤细胞(CTC)表达与胃癌根治手术患者预后结局的关系。方法:选取2014年1月至2018年6月在山东第一医科大学附属人民医院接受胃癌根治术治疗的139例患者作为研究对象,分别检测两组患者术前的外周血中CTC表达、mSEPT9表达水平,并比较不同临床病理学特征胃癌患者外周血中CTC、mSEPT9阳性表达率差异,计数资料采用率(%)描述,数据比较采用χ^(2)检验。采用生存曲线分析CTC、mSEPT9阳性与阴性表达患者的生存时间及生存率差异,并采用Cox多因素模型探讨CTC、mSEPT9与胃癌患者根治性手术后预后结局的关系。结果:139例接受胃癌根治术治疗的胃癌患者中,CTC检查阳性患者96例(69.06%)、阴性患者43例(30.94%);mSEPT9阳性52例(37.41%)、mSEPT9阴性患者87例(62.95%)。CTC阳性表达患者的5年生存率为27.08%(26/96),低于阴性表达患者46.51%(20/43)(χ^(2)=5.063,P<0.05),CTC阴性患者的生存时间中位数为56个月,长于阳性表达患者的47个月(Log rankχ^(2)=5.147,P<0.05);mSEPT9阳性表达患者的5年生存率为23.08%(12/52),低于阴性表达患者的39.08%(39/87)(Log rankχ^(2)=5.846,P<0.05),mSEPT9阴性患者的生存时间中位数为51个月,长于阳性表达患者的44个月(Log rankχ^(2)=5.846,P<0.05)。Cox回归模型结果显示,TNM分期为Ⅲ期(OR=1.749)、肿瘤低分化(OR=1.848)、浸润深度(T3+T4)(OR=1.597)、发生淋巴结转移(OR=2.036)、CTC阳性表达(OR=2.040)、mSEPT9阳性表达(OR=1.765)是胃癌根治术后患者5年随访不良预后的独立危险因素(P<0.05)。结论:接受胃癌根治术的患者外周血中的CTC、mSEPT9阳性表达率增高与疾病恶性程度有关,并且与患者术后不良预后结局关系密切。

Objective:To investigate the relationship between the expression of methylated Septin9 gene(mSEPT9)and circulating tumor cells(CTC)in peripheral blood and the prognosis of patients with gastric cancer undergoing radical surgery.Methods:A total of 139 patients who received radical gastrectomy in the Affiliated People’s Hospital of Shandong First Medical University from January 2014 to June 2018 were selected as the study objects,and the expression levels of CTC and mSEPT9 in peripheral blood of the two groups were detected before surgery.Furthermore,the difference in the positive expression rates of CTC and mSEPT9 in peripheral blood of gastric cancer patients with different clinically-pathological characteristics was compared,statistical data were described by using rate(%),and data were compared by means of the chi-square test.Survival curve was used to analyze the difference in survival time and survival rate between patients with positive and negative expression of CTC and mSEPT9.Cox multivariate model was used to explore the relationship between CTC and mSEPT9 and the prognosis of patients with gastric cancer after radical surgery.Results:Among 139 patients with gastric cancer who underwent radical gastrectomy,96(69.06%)were positive for CTC and 43(30.94%)were negative.There were 52(37.41%)MSEPT9-positive patients and 87(62.95%)MSEPT9-negative patients.The 5-year survival rate of patients with CTC-positive expression was 27.08%(26/96),which was lower than that of patients with negative expression (46.51%(20/43)(χ^(2)=5.063,P<0.05).The median survival time of patients with CTC-negative expression was 56 months.It was longer than 47 months in patients with positive expression(Log rankχ^(2)=5.147,P<0.05).The 5-year survival rate of patients with mSEPT9 positive expression was 23.08%(12/52),which was lower than that of patients with negative expression(39.08%(39/87)(Log rankχ^(2)=5.846,P<0.05).The median survival time of patients with mSEPT9 negative expression was 51 months.It was longer than 44 months in patients with positive expression(Log rankχ^(2)=5.846,P<0.05).Cox regression model results show that,TNM stageⅢ(OR=1.749),low tumor differentiation(OR=1.848),depth of invasion(T3+T4)(OR=1.597),lymph node metastasis(OR=2.036),positive expression of CTC(OR=2.040),and positive expression of mSEPT9(OR=1.765)were the results of radical resection of gastric cancer Independent risk factors for poor prognosis at 5-year follow-up(P<0.05).Conclusion:The increase in the positive expression rates of CTC and mSEPT9 in peripheral blood of patients undergoing gastric cancer radical surgery is related to the degree of malignancy of the disease,and is closely related to the adverse prognosis of patients after surgery.