血清miR-599联合VEGF预测分化型甲状腺癌患者次全切除术后复发的价值

Value of serum miR-599 combined with VEGF in predicting recurrence of patients with differentiated thyroid cancer after subtotal resection

目的分析血清微RNA-599(miR-599)联合血管内皮生长因子(VEGF)水平对分化型甲状腺癌(DTC)患者全腔镜甲状腺次全切除术后复发的预测效能。方法选取铜川市人民医院2017年1月至2022年3月收治的行全腔镜甲状腺次全切除术的DTC患者135例。患者术前均检测血清miR-599和VEGF水平,并收集患者术前临床相关资料。术后对患者进行为期2年的随访,根据术后复发情况将其分为复发组(31例)和无复发组(104例)。复发组男12例,女19例,年龄(51.26±7.32)岁;无复发组男48例,女56例,年龄(49.57±7.08)岁。计数资料采用χ^(2)检验或Fisher精确概率检验;计量资料采用独立样本t检验。患者术后复发的影响因素用多因素逐步logistic回归模型进行分析;血清miR-599联合VEGF水平预测患者术后复发的效能用受试者操作特征曲线(ROC)下面积(AUC)进行分析。结果复发组miR-599水平低于无复发组[(0.81±0.09)比(1.05±0.12)],VEGF水平高于无复发组[(32.55±5.26)ng/L比(24.83±4.07)ng/L](t=10.295、8.639,均P<0.001)。复发组Ⅲ~Ⅳ期占比[67.74%(21/31)比28.85%(30/104)]、抗甲状腺球蛋白抗体(TgAb)水平[(251.86±27.98)IU/ml比(211.43±23.49)IU/ml]高于无复发组,术中淋巴结清扫占比[22.58%(7/31)比44.23%(46/104)]、术后放射碘治疗占比[32.26%(10/31)比53.85%(56/104)]低于无复发组(t=8.040,χ^(2)=4.694、4.454,均P<0.05)。多因素逐步logistic回归分析显示,miR-599水平(OR=0.251,95%CI 0.109~0.576)是患者术后复发的独立保护因素,VEGF水平(OR=2.163,95%CI 1.256~3.722)、临床分期(OR=4.287,95%CI 1.908~9.631)、TgAb水平(OR=4.612,95%CI 2.172~9.789)是患者术后复发的独立危险因素(均P<0.05)。ROC显示,miR-599、VEGF及二者联合预测患者术后复发的灵敏度分别为71.00%、74.20%、90.30%,特异度分别为76.90%、72.10%、88.50%,AUC分别为0.824、0.794、0.931(均P<0.05)。结论血清VEGF水平是DTC患者全腔镜甲状腺次全切除术后复发的独立危险因素,血清miR-599水平是患者术后复发的独立保护因素;二者联合检测可较好地预测患者术后复发风险。

Objective To investigate the efficacy of serum microRNA-599(miR-599)and vascular endothelial growth factor(VEGF)levels in the prediction of recurrence of patients with differentiated thyroid cancer(DTC)after totally endoscopic subtotal thyroidectomy.Methods A total of 135 patients with DTC who underwent totally endoscopic subtotal thyroidectomy at Tongchuan People's Hospital from January 2017 to March 2022 were selected.The serum levels of miR-599 and VEGF in all the patients were detected before the operation.Their preoperative clinical data were collected.The patients were followed up for 2 years after the operation.According to the postoperative recurrence,they were divided into a recurrence group(31 cases)and a non-recurrence group(104 cases).There were 12 men and 19 women in the recurrence group;they were(51.26±7.32)years old.There were 48 men and 56 women in the non-recurrence group;they were(49.57±7.08)years old.The count data were analyzed byχ^(2) test or Fisher's exact probability test.The measurement data were analyzed by the independent-sample t test.The influencing factors of postoperative recurrence were analyzed by the multivariate stepwise logistic regression model.The predictive efficacies of serum miR-599 and VEGF levels in predicting postoperative recurrence were analyzed by the areas(AUC)under the receiver operating characteristic curves(ROC).Results The level of miR-599 in the recurrence group was lower than that in the non-recurrence group[(0.81±0.09)vs.(1.05±0.12)],and the level of VEGF in the recurrence group was higher than that in the non-recurrence group[(32.55±5.26)ng/L vs.(24.83±4.07)ng/L](t=10.295 and 8.639;both P<0.001).The proportion of the patients ofⅢ-Ⅳstage[67.74%(21/31)vs.28.85%(30/104)]and anti-thyroglobulin antibody(TgAb)level[(251.86±27.98)IU/ml vs.(211.43±23.49)IU/ml]in the recurrence group were higher than those in the non-recurrence groupm,and the proportions of the patients taking intraoperative lymph node dissection[22.58%(7/31)vs.44.23%(46/104)]and postoperative radioactive iodine therapy[32.26%(10/31)vs.53.85%(56/104)]in the recurrence group were lower than those in the non-recurrence group(t=8.040;χ^(2)=4.694 and 4.454;all P<0.05).The multivariate stepwise logistic regression analysis showed that the level of miR-599(OR=0.251,95%CI 0.109-0.576)was an independent protective factor for postoperative recurrence,and the level of VEGF(OR=2.163,95%CI 1.256-3.722),clinical stage(OR=4.287,95%CI 1.908-9.631),and TgAb level(OR=4.612,95%CI 2.172-9.789)were independent risk factors for postoperative recurrence(all P<0.05).The ROC showed that the sensitivities of miR-599,VEGF,and their combination in the prediction of postoperative recurrence were 71.00%,74.20%,and 90.30%,respectively;the specificities were 76.90%,72.10%,and 88.50%,respectively;the AUC's were 0.824,0.794,and 0.931,respectively(all P<0.05).Conclusions Serum VEGF level is an independent risk factor for recurrence,and serum miR-599 level is an independent protective factor for recurrence in DTC patients after total endoscopic subtotal thyroidectomy.The combined detection of the two markers can better predict the risk of postoperative recurrence.