循环miR-143水平在宫颈癌患者同步放化疗后肿瘤残留的早期预测

The value of circulating miR-143 level in predicting early response to concurrent chemoradiotherapy in cervical cancer patients

目的探讨血清miR-143水平结合MRI在预测宫颈癌同步放化疗(CCRT)早期反应的价值。方法收集85例经病理证实的宫颈癌患者,在CCRT前均行常规MRI、腔内非相干运动扩散加权成像(IVIM-DWI)和动态增强MRI(DCE-MRI),并收集患者的活检组织和血清样品。应用微阵列芯片分析活检组织中miRNA差异性表达。采用qRT-PCR分析血清样品中miR-143水平。根据术后MRI表现,将患者分为非残留肿瘤组和残留肿瘤组。对两组患者术前临床因素、MRI参数和miR-143进行单因素和多因素分析,绘制受试者工作曲线(ROC)曲线,估计治疗后残留肿瘤发生的最佳阈值和预测性能。结果CCRT完成后1个月,无残留组52例,残留组33例。残留组肿瘤的国际妇产科联合会分期、表观扩散系数、D和V^(e)明显高于非残留组(P<0.05),K^(trans)明显低于非残留组(P<0.001)。miRNA阵列分析显示两组间有16个miRNAs表达差异(P<0.05),其中miR-143的升高在残留组患者中最为显著。与残留组相比,非残留组的血清miR-143表达显著下调(P=0.002)。与Siha细胞相比,SiHa-R细胞的miR-143表达明显上调(P<0.05)。多因素分析显示只有miR-143、D、K^(trans)和V^(e)是独立的预后因素。ROC曲线分析显示MRI-miR-143组合参数的曲线下面积最高(AUC=0.975),敏感性为84.8%,特异性为96.2%。结论治疗前MRI参数与血清miR-143的结合进一步提高了CCRT后残留肿瘤的预测性能,有助于宫颈癌的个性化治疗。

Objective To investigate the value of serum miR-143 level combined with MRI in predicting the early response to concurrent chemoradiotherapy(CCRT)in cervical cancer.Methods A total of 85 patients with pathologically confirmed cervical cancer underwent conventional MRI,intravoxel incoherent motion diffusion-weighted imaging(IVIM-DWI),and dynamic contrast-enhanced MRI(DCE-MRI)before CCRT.The biopsy tissues and serum samples were collected.The differential expression of miRNA in the biopsy tissues was determined by microarray chip.The expression level of miR-143 in the serum samples was analyzed by qRT-PCR.All patients were divided into the non-residual and residual tumor groups according to post-treatment MRI.Pre-treatment clinical factors,MRI parameters and miR-143 between two groups were statistically analyzed by the univariate and multivariate analyses.The optimal thresholds and predictive performance for post-treatment incidence of residual tumors were estimated by drawing the ROC curve.Results At one month after CCRT,there were 52 patients in the non-residual tumor group and 33 patients in the residual tumor group.In the residual tumor group,pre-treatment FIGO staging,apparent diffusion coefficient(ADC),D and V^(e) were significantly higher(all P<0.05),whereas K^(trans) value was significantly lower(P<0.001)when compared to those in the non-residual tumor group.The miRNA array analysis showed that there were 16 miRNAs with differential expression levels between two groups(all P<0.05).Among them,the increase of miR-143 was the most significant in the residual tumor group.Compared with the residual tumor group,the expression level of serum miR-143 was significantly down-regulated in the non-residual tumor group(P=0.002).Compared with the SiHa cells,the expression level of miR-143 in the SiHa-R cells was significantly up-regulated(P<0.05).Multivariate analysis showed that only miR-143,D,K^(trans) and V^(e) were the independent prognostic factors.The combination of multi-parametric MRI and miR-143 exhibited the highest predictive performance(AUC=0.975),with a sensitivity of 84.8%and a specificity of 96.2%.Conclusion The combination of multi-parametric MRI with miR-143 further improves the predictive performance for residual tumors after CCRT,which contributes to the personalized treatment of cervical cancer.