局部晚期宫颈鳞状细胞癌血清外泌体miR-17-5p表达及临床意义

Expression and clinical significance of serumexosomal miR-17-5p in locally advanced cervical squamous cell carcinoma

目的 探讨血清外泌体miR-17-5p在局部晚期宫颈鳞状细胞癌(LACSCC)放疗随访中的临床价值。方法 选择2014年1月至2018年12月于我院进行放疗的146例LACSCC患者作为研究对象,采用实时荧光定量PCR(q PCR)检测患者放疗前后的血清外泌体miR-17-5p水平,其他潜在血清生物标志物包括放疗前后鳞状细胞癌抗原(SCC-Ag)、基质金属蛋白酶(MMP)-1和MMP-2。无进展生存期(PFS)为主要终点,总生存期(OS)为次要终点。结果 LACSCC患者放疗后的血清外泌体miR-17-5p水平显著低于基线值(P<0.05)。高表达组年龄>60岁、体质量指数>24.9 kg/m^(2)、国际妇产科联盟分期在Ⅲ~Ⅳa期的LACSCC患者比例更高(P<0.05)。基线血清外泌体miR-17-5p表达升高与PFS、OS较短有关(P<0.05)。Cox风险比例回归模型分析,最大肿瘤直径、基线血清SCC-Ag和外泌体miR-17-5p水平均是PFS及OS的独立预测因子(P<0.05)。经受试者工作特征曲线分析,基线血清外泌体miR-17-5p联合SCC-Ag水平预测LACSCC患者局部治疗失败或远处转移的曲线下面积分别为0.803(95%CI:0.704~0.901)、0.832(95%CI:0.756~0.908),优于SCC-Ag单独预测价值。结论 血清外泌体miR-17-5p可能是预测LACSCC患者放疗后生存结局的重要生物标志物。

Objective To investigate the clinical value of serum exosomal miR-17-5p in radiotherapy follow-up of locally advanced cervical squamous cell carcinoma(LACSCC).Methods A total of 146 patients with LACSCC who received radiotherapy in our hospital from January 2014 to December 2018 were selected as the research objects.Quantitative real-time polymerase chain reaction(qPCR)was used to detect the levels of serum exosomal miR-17-5p before and after radiotherapy.Other potential serum biomarkers include squamous cell carcinoma antigen(SCC-AG),matrix metalloproteinase(MMP)-1,and MMP-2 before and after radiotherapy.Progression-free survival(PFS)was the primary endpoint,and overall survival(OS)was the secondary endpoint.Results The level of serum exosomal miR-17-5p in LACSCC patients after radiotherapy was significantly lower than that at baseline(P<0.05).The proportion of LACSCC patients with age>60 years,body mass index>24.9 kg/m^(2),and International Federation of Obstetrics and Gynecology stage Ⅲ-ⅣA was higher in the high expression group(P<0.05).The increased expression of baseline exosomal miR-17-5p was associated with shorter PFS and OS(P<0.05).Cox proportional hazard regression model analysis showed that maximum tumor diameter,baseline serum SCC-Ag and exosomal miR-17-5p level were independent predictors of PFS and OS(P<0.05).According to receiver operating characteristic curve analysis,the area under the curve of baseline serum exosomal miR-17-5p combined with SCC-AG level in predicting local treatment failure or distant metastasis in LACSCC patients were 0.803(95%CI:0.704-0.901)and 0.832(95%CI:0.832),respectively.0.756-0.908),which was better than SCC-AG alone.Conclusion Serum exosomal miR-17-5p may be an important biomarker for predicting the survival outcome of LACSCC patients after radiotherapy.