外周血微RNA-122-5p和解整合素金属蛋白酶10在桥本甲状腺炎中的表达及临床意义

Expression and clinical significance of peripheral blood miR-122-5p and ADAM10 in patients with Hashimoto's thyroiditis

目的探究外周血微RNA-122-5p(miR-122-5p)和解整合素金属蛋白酶10(ADAM10)在桥本甲状腺炎(HT)病人中的表达情况及临床意义。方法选择2020年1月至2022年1月在南京医科大学第四附属医院经病理诊断的HT病人86例作为HT组,同期选择经甲状腺腺瘤切除手术的非癌病人62例作为对照组。收集两组病人的一般资料并检测甲状腺功能。实时荧光定量PCR(qRT-PCR)检测两组外周血中miR-122-5p表达水平,ELISA法检测两组外周血中ADAM10水平。Pearson法分析miR-122-5p或ADAM10水平与甲状腺功能参数的相关性。logistic回归分析模型评估HT的影响因素。ROC曲线用于评估miR-122-5p和ADAM10对HT发生的诊断价值。结果与对照组比较,HT组游离四碘甲状腺原氨酸(FT4)[(8.79±0.85)nmol/L比(13.15±1.21)nmol/L]、游离三碘甲状腺原氨酸(FT3)[(3.74±0.15)nmol/L比(4.56±0.24)nmol/L]水平及ADAM10表达[(3.21±1.13)μg/L比(5.02±1.69)μg/L]降低(P<0.05);促甲状腺激素(TSH)、甲状腺过氧化物酶抗体(TPOAb)、甲状腺球蛋白抗体(TGAb)、C反应蛋白(CRP)水平及miR-122-5p表达(1.57±0.46比1.02±0.34)均升高(P<0.05)。HT组和对照组miR-122-5p与TGAb、TPOAb、CRP水平呈正相关(P<0.05);ADAM10与TGAb、TPOAb及CRP均呈负相关(P<0.05)。HT组中miR-122-5p与ADAM10水平呈负相关(r=−0.46,P<0.05)。MiR-122-5p、ADAM10、TGAb和TPOAb是HT发生的影响因素(P<0.05)。MiR-122-5p、ADAM10及二者联合区分HT组和对照组的最佳截断值分别为1.22、4.74μg/L、0.42,曲线下面积分别为0.83(0.76,0.89)、0.85(0.78,0.90)、0.91(0.85,0.95)。结论HT病人外周血中miR-122-5p表达升高,ADAM10水平降低,二者与甲状腺微结构损伤有关,且对HT的早期诊断具有一定价值。

Objective To investigate the expression and clinical significance of peripheral blood microRNA-122-5p(miR-122-5p)and a disintegrin and metalloproteinase 10(ADAM10)in patients with Hashimoto's thyroiditis(HT).Methods From January 2020 to January 2022,86 HT patients who were pathologically diagnosed in the Fourth Afiliated Hospital of Nanjing Medical University were regarded as the HT group.During the same period,62 non-cancer patients who underwent thyroid adenoma resection were regarded as the control group.The general data of patients in the two groups were collected and thyroid function parameters were detected.Quantitative real-time PCR(qRT-PCR)was applied to analyze the expression level of miR-122-5p in the peripheral blood of the two groups,and ELISA was used to detect the level of ADAM10 in peripheral blood of the two groups.Pearson method was applied to analyze the correlation of miR-122-5p or ADAM10 levels with thyroid function parameters.logistic regression analysis model was applied to evaluate the influencing factors of HT.ROC curve was used to evaluate the discriminative value of miR-122-5p and ADAM10 for the HT group and the control group.Results Compared with the control group,the levels of free thyroxin(FT4)[(8.79±0.85)nmol/L vs.(13.15±1.21)nmol/L],free triiodothyronine(FT3)[(3.74±0.15)nmol/L vs.(4.56±0.24)nmol/L]and the expression of ADAM10[(3.21±1.13)μg/L vs.(5.02±1.69)μg/L]in the HT group were decreased(P<0.05);the levels of thyroid-stimulating hormone(TSH),thyroid peroxidase antibody(TPOAb),thyroglobulin antibody(TGAb),C-reactive protein(CRP)and miR-122-5p expression(1.57±0.46 vs.1.02±0.34)were all increased(P<0.05).MiR-122-5p was positively correlated with the levels of TGAb,TPOAb and CRP in HT group and control group(P<0.05);ADAM10 was negatively correlated with TGAb,TPOAb and CRP(P<0.05).There was a negative correlation between miR-122-5p and ADAM10 levels in the HT group(r=−0.46,P<0.05).MiR-122-5p,ADAM10,TGAb and TPOAb were the influencing factors of HT(P<0.05).The optimal cutoff values for distinguishing between the HT group and the control group were 1.22,4.74μg/L,and 0.42 for MiR-122-5p,ADAM10,and their combination.The area under the curve was 0.83(0.76,0.89),0.85(0.78,0.90),and 0.91(0.85,0.95),respectivelyConclusion The expression of miR-122-5p in peripheral blood of HT patients is increased,and the level of ADAM10 is decreased,both of which are related to thyroid microstructure damage,and have certain value for the early diagnosis of HT.