血清miR-218作为局部晚期宫颈癌同步放化疗反应及预后标志物的临床价值

Clinical value of serum miR-218 as a marker of tumor response and prognosis in locally advanced cervical cancer with concurrent chemoradiation

目的:分析局部晚期宫颈癌(LACC)患者血清miR-218表达与同步放化疗(CCRT)反应及预后的相关性。方法:收集2016年3月至2021年7月在南通大学附属肿瘤医院妇瘤科接受CCRT的142例LACC患者;采用实时荧光定量聚合酶链反应检测患者血清miR-218表达;根据治疗期间病情是否进展或治疗结束后12个月内是否复发将患者分为敏感组(n=114)和耐药组(n=28);随访观察主要终点为无进展生存期(PFS);次要终点包括总生存期(OS)、盆腔PFS(PPFS)和无远处转移生存期(DMFS)。结果:LACC患者血清miR-218水平为0.85(0.49,1.06);耐药组患者血清miR-218表达低于敏感组[0.29(0.21,0.41)vs.0.92(0.73,1.06),P<0.001],且血清miR-218用于预测CCRT耐药的受试者工作特征曲线下面积(AUC)为0.941(95%CI:0.904~0.979),相对于鳞状细胞癌抗原(SCC-Ag),miR-218可能是预测CCRT耐药的更有效工具(P<0.05)。Kaplan-Meier生存曲线显示,血清miR-218低表达与LACC患者PFS、OS、PPFS、DMFS较短有关(Log rankχ^(2)=52.232,20.512,24.185,34.897,均P<0.05)。经单因素及多因素COX模型分析,血清miR-218表达为与LACC患者PFS、OS、PPFS、DMFS相关的预后因素(P<0.001)。结论:CCRT耐药的LACC患者中血清miR-218表达下调,miR-218表达是LACC的一个预后因素。

Objective:To analyze the correlation among serum miR-218 expression,concurrent chemoradiotherapy(CCRT)response and prognosis in patients with locally advanced cervical cancer(LACC).Methods:A total of 142 LACC patients who received CCRT in the Department of Gynecological oncology of Tumor Hospital Affiliated to Nantong University from March 2016 to July 2021 were included.The expression of miR-218 in patients’serum was detected by real-time quantitative polymerase chain reaction.The patients were divided into sensitive group(n=114)and drug resistant group(n=28)based on whether the disease progressed during treatment or the disease recurred within 12 months after treatment.The primary end points of follow-up were progression-free survival(PFS),and the secondary end points included overall survival(OS),pelvic PFS(PPFS)and distant metastasis free survival(DMFS).Results:The serum miR-218 level in LACC patients was 0.85(0.49,1.06).The expression of serum miR-218 in drug-resistant group was lower than that in sensitive group[0.29(0.21,0.41)vs.0.92(0.73,1.06),P<0.001].The area under the receiver operating characteristic curve(AUC)of serum miR-218 for predicting CCRT-resistance was 0.941(95%CI:0.904-0.979).Compared with SCC-Ag,mir-218 may be a more effective tool for predicting CCRT-resistance(P<0.05).Kaplan-Meier survival showed that the low expression of serum miR-218 was associated with shorter PFS,OS,PPFS and DMFS in LACC patients(Log rankχ^(2)=52.232,20.512,24.185,34.897,P<0.05).Univariate and multivariate COX model analysis showed that serum miR-218 expression was still an indepen-dent prognostic factor associated with PFS,OS,PPFS and DMFS in patients with LACC(P<0.001).Conclusion:Serum miR-218 expression is down-regulated in patients with CCRT-resistant LACC,so serum miR-218 expression is an independent prognostic factor for LACC.