结直肠癌术后循环肿瘤细胞检测的临床意义

Clinical significance of detection of circulating tumor cells after colorectal cancer surgery

目的探讨结直肠癌(CRC)患者术后外周血循环肿瘤细胞(CTCs)阳性率及其计数与临床病理特征、肿瘤复发转移及预后之间的关系及其临床意义。方法回顾性分析2016年1月—2017年7月上海交通大学医学院附属第九人民医院首诊并经病理确诊的99例CRC患者的临床资料,其中男66例、女33例,年龄37~79岁。检测患者术后4~8周且辅助治疗前CTCs计数和血清癌胚抗原(CEA)水平,随访患者生存情况,比较患者不同临床病理学特征患者间CTCs表达及计数值的统计学差异,包括性别、年龄、原发灶部位、肿瘤分化程度、原发灶浸润深度(T分期)、区域淋巴结侵袭程度(N分期)、远处转移(M分期)、TNM总分期;观察患者生存情况;采用COX比例风险回归模型进行无进展生存期、总生存期的单因素和多因素分析。结果99例CRC患者CTCs阳性率为60.6%(60/99),CTCs计数值为0~24(4.909±5.518)。患者的CTCs阳性率和CTCs计数值在T1+T2+T3期、N0期、M0期、Ⅰ~Ⅱ期、CEA<5 ng/mL和中高分化组患者低于T4期、N1+N2期、M1期、Ⅲ~Ⅳ期、CEA≥5 ng/mL、低分化组患者,差异均有统计学意义(P值均<0.05)。患者随访3~20个月,死亡22例(22/99,22.2%),其中CTCs阳性21例;疾病进展32例(32/99,32.3%),其中CTCs阳性29例。单因素分析显示:CTCs表达、N分期、M分期、肿瘤分期、和高CEA水平是无进展生存期的影响因素(P值均<0.05);CTCs表达、N分期、M分期、肿瘤原发灶位于直肠、高CEA水平是总生存期的影响因素(P值均<0.05)。CTCs和远处转移是CRC患者无进展生存期和总生存期的独立预后因素(HR=5.418、2.254,95%可信区间:1.595~8.403、1.227~7.986,P值均<0.05)。结论在术后CRC患者中,CTCs表达与预后不良有关,对肿瘤复发转移评估具有一定的价值和临床意义。

Objective To evaluate the relationship between peripheral blood circulation tumor cells(CTCs)and clinical pathological variables,tumor recurrence and metastasis and prognosis in patients with colorectal cancer(CRC).Methods From January 2016 to July 2017,the clinical pathological variables of 99 newly-diagnosed and histopathologically confirmed CRC patients from the Ninth People's Hospital affiliated to Shanghai jiao tong university medical school were collected.There were 66 males and 33 females,aged 37-79 years old.The CTCs enumeration and the serum carcinoembryonic antigen(CEA)levels were measured between 4 and 8 weeks after surgery or before adjuvant therapy.All patients were followed up for survival.Statistical differences in characteristics and CTCs enumeration,including gender,age,primary site,tumor differentiation,primary invasive depth(T stage),regional lymph node invasion(N stage),distant metastasis(M Staging),TNM staging,observation of patient survival,COX proportional hazards regression model for single-factor and multivariate analysis of progression-free survival and overall survival.Results The positive rate of CTCs in 99 CRC patients was 60.6%(60/99),and the range of CTCs was 0-24(4.909±5.518).CTCs in patients with positive expression and CTCs count stage T1+T2,T3,N0,M0,Ⅰ-Ⅱperiod,the CEA<5 ng/mL were lower than those of T4,N1+N2,M1 period,Ⅲ-Ⅳperiod,the CEA acuity 5 ng/mL,low differentiation,and the differences were statistically significant(all P values<0.05).The patients were followed up for 3 to 20 months,and 22 patients died(22/99,22.2%),including 21 CTCs positive;32 patients with disease progression(32/99,32.3%),of which 29 were positive for CTCs.Univariate analysis showed that CTCs,N stage,M stage,tumor stage,and high serum CEA levels were the influencing factors of poor progression-free survival(all P values<0.05).CTCs,N stage,M stage,primary tumor stage and high CEA levels were the influencing factors of poor overall survival(all P values<0.05).CTCs and distant metastasis were independent prognostic factors for poor progression-free survival and overall survival in CRC patients(HR=5.418,2.254,95%confidence interval:1.595-8.403,1.227-7.986,all P values<0.05).Conclusions In patients with postoperative CRC,CTCs enumeration might be a predictive factor for tumor recurrence and metastasis.CTCs positive might be associated with a reduced survival in patients with colorectal cancer.