循环肿瘤细胞评估甲状腺髓样癌预后的应用价值初步研究

Preliminary study on the application value of circulating tumor cells in evaluating the prognosis of medullary thyroid carcinoma

目的:探讨循环肿瘤细胞(CTC)作为评估甲状腺髓样癌(MTC)预后的新型生物标志物的应用价值。方法:回顾分析2016年1月至2019年1月间南京医科大学附属淮安第一医院收治的36例MTC患者的资料,通过CellSearch系统检测治疗前MTC患者CTC浓度,以每7.5 ml血液CTC计数≥1为阳性。分析CTC与患者年龄、性别、肿瘤类型、基因突变位点、肿瘤分化程度、肿瘤异型性、癌胚抗原(CEA)、降钙素(Ct)及TNM分期的关系。比较CTC阳性和阴性两组MTC患者的无进展生存期(PFS)和总生存期(OS),Cox回归模型分析生存时间的影响因素。结果:36例MTC患者中21例有CTC,阳性率为58.3%,CTC与患者年龄、性别、肿瘤类型、基因突变位点、肿瘤分化程度及异型性无关(P>0.05),与TNM相关(P<0.05)。CTC阳性MTC患者CEA和Ct表达均高于CTC阴性患者(P<0.05)。与CTC阴性患者相比,CTC阳性患者PFS和OS较短(P<0.05),提示CTC≥1是影响MTC预后的独立危险因素(HR=5.13,95%CI为3.72~9.52,P=0.028)。Cox回归模型分析显示TNM分期、CEA及Ct是影响MTC预后的危险因素。结论:CTC与TNM分期、CEA、Ct相关,CTC阳性的MTC患者PFS和OS较短,预后较差,CTC具有评估甲状腺髓样癌预后的潜力;TNM分期、CEA、Ct高水平及CTC阳性是影响甲状腺髓样癌预后的危险因素。

Objective:To investigate the application value of circulating tumor cells(CTC)as a new biomarker for the prognosis of patients with medullary thyroid carcinoma(MTC).Methods:A retrospective analysis of 36 patients with medullary thyroid cancer treated in Huai'an First Hospital Affiliated to Nanjing Medical University from January 2016 to January 2019 was conducted.CellSearch system was used to detect the concentration of circulating tumor cells in patients with medullary thyroid cancer before treatment,and the concentration of CTC≥1·7.5 ml^(-1) was defined as CTC-positive.The relationship between the CTC and age,gender,gene mutation site,tumor differentiation degree,tumor atypia,carcino-embryonic antigen(CEA),calcitonin(Ct),TNM stage was analyzed.Comparison of the survival time(progression-free survival time(PFS)and overall survival time(OS))of the two groups of MTC patients with CTC positive and negative was performed.Cox regression model was used to analyze the influencing factors of the survival time.Results:Twenty-one of the 36 MTC patients had CTC,and the CTC-positive rate was 58.3%.CTC was not related to age,gender,gene mutation site,tumor differentiation and atypia(P>0.05),but related to TNM(P<0.05).The expressions of CEA and Ct in CTC-positive MTC patients were higher than those of CTC-negative patients,and the difference was statistically significant(P<0.05).Compared with CTC-negative patients,CTC-positive MTC patients had shorter PFS(P<0.05)and OS(P<0.05),suggesting that CTC≥1 was an independent factor affecting the prognosis of medullary thyroid carcinoma(HR=5.13,95%CI 3.72-9.52,P=0.028).The results of Cox regression model showed that TNM staging,CEA and Ct were risk factors that affected the prognosis of patients with medullary thyroid cancer.Conclusion:CTC is related to TNM staging,CEA,and Ct.CTC-positive MTC patients have much shorter PFS and OS,and poor prognosis,suggesting that CTC has the potential to assess the prognosis of patients with medullary thyroid cancer.TNM staging,high levels of CEA and Ct,positive CTC are risk factors that affect the prognosis of patients with medullary thyroid carcinoma.