早中期结直肠癌手术前后外周血循环肿瘤细胞的监测及预后分析  

Monitoring and Prognostic Analysis of Peripheral Blood Circulating Tumor Cell Before and After Operation for Early and Middle Stage Colorectal Cancer

作　　者：曹霞 吴伟 赵小玉 李曾 韩亚兵 李翔 田姗 张丹[1] CAO Xia;WU Wei;ZHAO Xiao-yu;LI Zeng;HAN Ya-bing;LI Xiang;TIAN Shan;ZHANG Dan(Department of Medical Oncology,3201 Hospital of Xi′an Jiaotong University Health Science Center,Hanzhong 723000,China;Department of General Surgery,3201 Hospital of Xi′an Jiaotong University Health Science Center,Hanzhong 723000,China;State Key Laboratory of Genetic Laboratory Engineering,School of Life Sciences,Fudan University,Shanghai 200433,China;Biotencan Medical Diagnostics Co.,Ltd,Shanghai 201204,China)

机构地区：[1]西安交通大学医学部附属三二〇一医院肿瘤内科,陕西汉中723000 [2]西安交通大学医学部附属三二〇一医院胃肠外科,陕西汉中723000 [3]复旦大学生命科学学院遗传工程国家重点试验室,上海200433 [4]上海宝藤生物医药科技股份有限公司,上海201204

出　　处：《中山大学学报（医学版）》2019年第4期604-614,共11页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：国家自然科学基金(81572358,81572332,81201936)

摘　　要：【目的】通过动态监测早中期结直肠癌患者手术前后外周血循环肿瘤细胞(CTC)的变化,研究外周血CTC与临床病理特征的关系,并评估外周血CTC在早中期结直肠癌中的诊断和预后预测价值。【方法】本研究前瞻性地纳入67例早中期结直肠癌患者,同期收集20例健康志愿者作为对照组。分别采集患者根治性手术前24h、术后3个月以及对照组的外周静脉血(7.5mL),采用差减富集-免疫荧光原位杂交(SE-iFISH)技术分离和鉴定CTC。利用受试者工作曲线(ROC)及约登指数判定CTC诊断结直肠癌的临界值,采用Kaplan-Meier和Log-rank方法进行生存分析,多因素COX回归分析进行多因素校正,综合评估CTC诊断早中期结直肠癌的价值,然后结合临床病理特征以及术后随访资料,分析外周血循环肿瘤细胞与临床病理特征及预后的关系。【结果】早中期结直肠癌患者CTC阳性率显著高于健康人(91.0%vs.5.0%,P<0.01)。术后CTC的数值与侵袭深度及肿瘤部位显著有关(P=0.001;P=0.044),与性别、年龄、肿瘤大小、淋巴结转移、TNM分期、CEA水平以及CA-199水平无相关性。术前CTC的数值与上述临床病理参数均不相关。术前CTC对无病生存期(DFS)和总生存期(OS)无预测意义(AUC=0.359,P=0.068;AUC=0.428,P=0.423);术后CTC临界点为3个/7.5mL对DFS和OS有预测意义(AUC=0.936,P<0.001;AUC=0.863,P<0.001)。早中期结直肠癌术后分为良好预后组(术后CTC<3或者术后CTC数目比术前CTC数目减少或持平)和不良预后组(术后CTC≥3或者术后CTC数目比术前CTC数目增加),良好预后组的DFS较不良预后组显著延长(43.7月vs.20.4月,P<0.001;48.7月vs.26.8月,P<0.001),并且总生存期(OS)也显著延长(54.4月vs.43.3月,P<0.001;54.8月vs.45.1月,P<0.001)。多因素分析发现术后CTC≥3个/7.5mL是DFS和OS的不良独立因素。【结论】CTC在早中期结直肠癌患者中具有较高的临床诊断价值。术前CTC数值不能预测早中期结直�【Objective】To study the relationship between circulation tumor cell(CTC)and clinicopathological characteristics in early and middle stage colorectal cancer,and to evaluate the diagnostic and prognostic value of peripheral blood CTC through dynamically monitoring the changes of peripheral blood CTC in the patients before and after operation.【Methods】Prospectively 67 patients with early and middle stage colorectal cancer were included,and 20 healthy volunteers served as contrast during the same period.Peripheral venous blood(7.5 mL)was collected 24 h before radical operation,3 months after radical operation and in control group.SE-iFISH technique was used to isolate and identify CTC.The cutoff value of CTC in diagnosis of colorectal cancer was determined by the receiver operating curve(ROC)and Youden index.Kaplan-Meier and log-rank methods were used for survival analysis and multivariate COX regression analysis for multivariate correction.The value of CTC in the diagnosis of early and middlestage colorectal cancer was evaluated comprehensively,and then the relationship between CTC in peripheral blood and clinicopathological characteristics and prognosis was synthetically evaluated combined with clinicopathological characteristics and postoperative follow-up data.【Results】The positive rate of CTC in patients with early and middle stage colorectal cancer was significantly higher than that in healthy people(91.0% vs.5.0%,P < 0.01).The CTC enumeration was significantly correlated with the depth of invasionand tumor location(P = 0.001,P = 0.044),but not with gender,age,tumor size,lymph node metastasis,TNM stage,CEA level and CA-199 level.The preoperative CTC enumeration were not correlated with the above-mentioned clinicopathological parameters.Preoperative CTC had no predictive significance for disease free survival(DFS)and total survival(OS)(AUC = 0.359,P = 0.068;AUC = 0.428,P = 0.423),and postoperative CTC critical point of 3/7.5 mL had predictive significance for DFS and OS(AUC = 0.936,P < 0.001;AUC = 0.

关 键 词：结直肠癌 手术 循环肿瘤细胞 预后 

分 类 号：R73[医药卫生—肿瘤]