循环肿瘤细胞、miR-100、鳞状细胞癌抗原与局部晚期宫颈癌放疗患者生存预后的关系研究

Relationship Between Circulating Tumor Cell,miR-100,Squamous Cell Carcinoma Antigen and Survival Outcomes in Patients Treated with Radiotherapy for Locally Advanced Cervical Cancer

目的评估循环肿瘤细胞(circulating tumor cells,CTC)、miR-100联合鳞状细胞癌抗原(squamous cell carcinoma antigen,SCC-Ag)检测对局部晚期宫颈癌(locally advanced cervical cancer,LACC)放疗患者预后的影响。方法选择2017-01/2022-04月作者医院145例接受放疗或同步放化疗(concurrent chemoradiotherapy,CCRT)的LACC患者为研究对象。检测初次就诊时CTC、miR-100水平与临床病理参数之间的关系。使用Cox比例风险回归模型进行单变量和多变量生存分析。随访主要终点为无进展生存期(progression-free survival,PFS),次要终点包括总生存期(overall survival,OS)、骨盆PFS(pelvic progression-free survival,PPFS)和远处无转移生存期(distant metastasis-free survival,DMFS)。结果145例LACC患者CTC的阳性率为55.86%(81/145),即CTC≥3 CTC/3.2 ml。放疗前miR-100水平为0.23(0.18,0.29)。miR-100<0.23的患者国际妇产科联盟(international federation of obstetrics and gynecology,FIGO)Ⅲ~ⅣA期比例更高(P=0.004),CTC≥3 CTC/3.2 ml的LACC患者的肿瘤直径更大(P=0.032)。42例(28.97%)患者获得疾病进展。受试者工作特征(receiver operating characteristic,ROC)曲线分析显示,SCC-Ag、CTC和miR-100预测LACC进展的最佳截断值为4.35 ng/ml、4.50 CTC/3.2 ml和0.23,三者联合预测疾病进展的灵敏度和特异度分别为73.80%和75.70%。SCC-Ag水平升高、CTC增加、miR-100水平降低与LACC患者PFS、OS、PPFS、DMFS较差有关(P<0.05)。多变量分析表明,SCC-Ag、CTC、miR-100是PFS的独立危险因素(P<0.05)。结论SCC-Ag、CTC和miR-100是预测LACC患者预后的潜在生物标志物,三者联合检测可显著提高LACC患者生存预测能力。

Objective To evaluate the effects of circulating tumor cells(CTC)and miR-100 combined squamous cell carcinoma antigen(SCC-Ag)detection on the prognosis of patients with locally advanced cervical cancer(LACC)treated with radiotherapy.Methods A total of 145 patients with LACC received radiotherapy or concurrent chemoradiotherapy(CCRT)were selected from January 2017 to April 2022.The relationship between CTC,miR-100 level and clinicopathologic parameters at first visit was detected.Univariate and multivariate survival analysis were performed by Cox proportional hazard regression models.The primary endpoint of follow-up was progression-free survival(PFS),and secondary endpoints included overall survival(OS),pelvic progression-free survival(PPFS)and distant metastasis-free survival(DMFS).Results The positive rate of CTC in 145 LACC patients was 55.86%(81/145),that is,CTC≥3 CTC/3.2 ml.The miR-100 level before radiotherapy was 0.23(0.18,0.29).Patients with miR-100<0.23 had a higher proportion of international federation of obstetrics and gynecology(FIGO) Ⅲ to Ⅳ at A stage(P=0.004),the tumor diameter was larger in LACC patients with CTC≥3 CTC/3.2 ml(P=0.032).Forty-two patients(28.97%)achieved disease progression in this study.The best cut-off values for SCC-Ag,CTC and miR-100 predicting LACC progression were 4.35 ng/ml,4.50 CTC/3.2 ml and 0.23 respectively according to the analysis of receiver operating characteristic(ROC)curve.The sensitivity and specificity for predicting disease progression were 73.80% and 75.70% respectively.Increasing SCC-Ag level,increasing CTC and decreasing miR-100 level were associated with poor PFS,OS,PPFS and DMFS in LACC patients(P<0.05).Multivariate progression showed that SCC-Ag,CTC and miR-100 were independent risk factors for PFS(P<0.05).Conclusion SCC-Ag,CTC and miR-100 are potentially biomarkers for predicting the prognosis of LACC patients,and the joint detection of the three can significantly improve the ability to predict the survival of LACC patients.