血清miR-21、miR-221、miR-146a变化与甲状腺癌结构性复发相关性研究

Relevance between changes in serum miR-21,miR-221 and miR-146a levels and structural recurrence of thyroid cancer

目的探究miR-21、miR-221、miR-146a水平变化与甲状腺癌结构性复发的相关性,以期为甲状腺癌的复发监测提供可能的生物学标志物。方法选取2019-05-03-2021-05-10郑州市中心医院收治的分化型甲状腺癌患者88例,根据是否发生结构性复发进行分组,其中复发组28例,未复发组60例,另纳入同期来本院行体检的45名健康体检者作为对照组。收集患者资料,采用聚合酶链反应-限制片段长度多态检测miR-21、miR-221、miR-146a表达水平,比较3组miRNA表达情况;通过Logistic分析影响甲状腺癌结构性复发的单因素和多因素;Pearson分析miR-21、miR-221、miR-146a与甲状腺球蛋白的相关性;并采用MedCalc绘制ROC曲线分析miR-21、miR-221、miR-146a对甲状腺癌复发的预测价值。结果复发组miR-21(3.05±1.03)、miR-221(2.80±0.96)水平高于未复发组(1.15±0.33)、(1.10±0.23),miR-146a(0.85±0.21)水平低于未复发组(1.11±0.45),差异有统计学意义,F值分别为184.838、273.157和62.630,均P<0.05。年龄≥50岁(OR=1.446,95%CI为1.061~1.971)、肿瘤长径≥2 cm(OR=1.533,95%CI为1.111~2.114)、包膜侵犯(OR=1.687,95%CI为1.017~2.797)、临床分期Ⅲ~Ⅳ(OR=1.614,95%CI为1.184~2.200)、淋巴结转移(OR=1.679,95%CI为1.296~2.174)、术后无辅助治疗(OR=1.374,95%CI为1.053~1.764)、miR-21(OR=1.581,95%CI为1.111~2.250)、miR-221(OR=2.002,95%CI为1.273~3.148)、miR-146a(OR=1.539,95%CI为1.200~1.974)过表达是结构性复发的独立危险因素,差异有统计学意义,均P<0.05。miR-21和miR-221过表达与分化型甲状腺癌结构性复发呈正相关(r=0.738和0.550,均P<0.05),miR-146a过表达与分化型甲状腺癌结构性复发呈负相关,r=-0.726,P<0.05。miR-21、miR-221、miR-146a联合预测的灵敏度与特异度分别为92.86%和85.00%,均高于各指标单一诊断的灵敏度与特异度,差异有统计学意义,Z值分别为2.438、2.122和2.758,P值分别为0.015、0.034和0.006。结论miR-21、miR-221、miR-146a水平变化均与分化型甲状腺癌结构性复发密切相关,三者水平的过表达是影响患者复发的独立危险因素,联合检测可提高甲状腺癌结构性复发的预测价值。

Objective To explore the correlation between changes in miR-21,miR-221 and miR-146 a levels and structural recurrence of thyroid cancer,so as to provide possible biomarkers for recurrence monitoring of thyroid cancer.Methods A total of 88 patients with differentiated thyroid cancer who were admitted to Zhengzhou Central Hospital from May 3,2019 to May 10,2021 were selected.They were divided into recurrence group(28 cases)and non-recurrence group(60 cases)according to the presence or absence of structural recurrence.Meanwhile,45 healthy individuals were selected as the control group.The patients’data were collected,and the expression levels of miR-21,miR-221 and miR-146 a were detected by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP).The expression of miRNAs in the 3 groups was compared.Univariate analysis and multivariate Logistic analysis were performed to screen the factors affecting structural recurrence of thyroid cancer.Pearson analysis was performed to clarify the correlation between miR-21,miR-221,miR-146 a and thyroglobulin.MedCalc was used to plit ROC curve to analyze the value of miR-21,miR-221 and miR-146 a in predicting recurrence of thyroid cancer.Results The levels of miR-21 and miR-221 in the recurrence group[(3.05±1.03)and(2.80±0.96)]were higher than those in the non-recurrence group[(1.15±0.33)and(1.10±0.23)],and the miR-146 a level(0.85±0.21)was lower than that in the non-recurrence group(1.11±0.45).The differences were statistically significant(F=184.838,273.157,62.630,all P<0.05).Age≥50years(OR=1.446,95%CI was 1.061-1.971),tumor diameter≥2cm(OR=1.533,95%CI was 1.111-2.114),capsular invasion(OR=1.687,95%CI was1.017-2.797),clinical stageⅢ-Ⅳ(OR=1.614,95%CI was 1.184-2.200),lymph node metastasis(OR=1.679,95%CI was 1.296-2.174),no adjuvant treatment after surgery(OR=1.374,95%CI was 1.053-1.764),overexpression of miR-21(OR=1.581,95%CI was 1.111-2.250),miR-221(OR=2.002,95%CI was 1.273-3.148)and miR-146a(OR=1.539,95%CI was 1.200-1.974)were independent risk factors of structural recurrence(all P<0.05).The overexpressions of miR-21and miR-221 were positively correlated with structural recurrence of differentiated thyroid cancer(r=0.738,0.550,both P<0.05),and the overexpression of miR-146awas negatively correlated with structural recurrence of differentiated thyroid cancer(r=-0.726,P<0.05).The sensitivity and specificity of combined prediction of miR-21,miR-221and miR-146awere 92.86%and 85.00%,higher than those of single diagnosis of each index(Z=2.438,2.122,2.758,P=0.015,0.034,0.006).Conclusions The changes in levels of miR-21,miR-221and miR-146aare closely related to structural recurrence of differentiated thyroid cancer.Overexpression of the three is an independent risk factor for recurrence.Joint detection of the three can improve the prediction of structural recurrence of thyroid cancer.