外周血微小RNA表达与甲状腺激素水平的关联及对甲状腺功能异常的预测效能分析

doi:10.3760/cma.j.issn.1007-1245.2023.24.011

摘要/Abstract

摘要：

目的　分析外周血微小RNA（micro ribonucleic acid，miRNA）表达与甲状腺激素水平的关联及对甲状腺功能异常的预测效能。方法　选取2021年1月至2022年12月于南阳医学高等专科学校附属中医院接受治疗的126例甲状腺功能异常患者作为研究对象，根据甲状腺激素水平不同将患者分为甲亢组［60例，男35例，女25例，年龄（55.25±5.61）岁］、甲减组［66例，男36例，女30例，年龄（56.16±5.28）岁］。比较两组患者甲状腺激素水平以及外周血miRNA-192、miRNA-21相对表达量。Spearman相关性分析各miRNA相对表达量与各甲状腺激素水平的相关性；通过绘制受试者工作特征曲线（receiver operating characteristic curve，ROC）验证miRNA表达对甲状腺功能异常的预测效能。采用χ²检验和t检验。结果　甲亢组患者的促甲状腺激素（thyroid-stimulating hormone，TSH）水平为（1.25±0.16）mU/L，低于甲减组的（4.86±1.33）mU/L，游离甲状腺激素3（free thyroid hormones 3，FT3）水平为（12.44±4.28）pmol/L，FT4水平为（25.35±10.46）pmol/L，总三碘甲状腺原氨酸（total thyroid triiodothyronine 3，TT3）水平为（6.62±2.41）nmol/L，总甲状腺素（total thyroxine，TT4）水平为（182.44±50.47）nmol/L，均高于甲减组［（5.16±1.44）pmol/L、（17.44±5.49）pmol/L、（2.25±0.46）nmol/L、（121.44±50.72）nmol/L］，差异均有统计学意义（t=20.880、13.035、5.383、14.450、6.758；均P<0.05）。甲亢组miRNA-192相对表达量为（0.34±0.11），低于甲减组的（0.92±0.45），miRNA-21相对表达为（0.61±0.23），高于甲减组的（0.22±0.07），差异均有统计学意义（t=9.720、13.128；均P<0.05）。Spearman相关性分析结果显示，miRNA-192与TSH正相关，与FT3、FT4、TT3、TT4负相关；miRNA-21与TSH负相关，与FT3、FT4、TT3、TT4正相关。经ROC验证，miRNA-192相对表达量会随TSH降低以及FT3、FT4、TT3、TT4升高而下降；miRNA-21相对表达量会随TSH降低以及FT3、FT4、TT3、TT4升高而上升。结论　外周血miRNA相对表达量与甲状腺激素水平变化密切相关，对甲状腺功能亢进或甲状腺功能减退均具有较高预测效能。

关键词:

甲状腺功能异常, 甲状腺激素, 外周血微小RNA, 相关性, 预测效能

Abstract:

Objective　To analyze the correlation between the expressions of micro ribonucleic acid (miRNA) in peripheral blood and the levels of thyroid hormones, and to predict thyroid dysfunction. Methods　One hundred and twenty-six patients with thyroid dysfunction who were treated in Hospital of Traditional Chinese Medicine Affiliated to Nanyang Medical College from January 2021 to December 2022 were selected as the research objects. According to the different levels of thyroid hormones, the patients were divided into a hyperthyroidism group (60 cases), including 35 males and 25 females who were (55.25±5.61) years old, and a hypothyroidism group (66 cases), including 36 males and 30 females who were (56.16±5.28) years old. The levels of thyroid hormones and the relative expressions of miRNA-192 and miRNA-21 in peripheral blood were compared between the two groups. Spearman correlation analysis was used to analyze the correlation between the relative expressions of miRNAs and the levels of thyroid hormones. The predictive efficacy of miRNA expression on thyroid dysfunction was verified by drawing receiver operating characteristic curves (ROC). χ² and t tests were applied. Results　The levels of thyroid-stimulating hormone (TSH), free thyroid hormones 3 (FT3), FT4, total thyroid triiodothyronine 3 (TT3), and total thyroxine (TT4) in the hyperthyroidism group were (1.25±0.16) mU/L, (12.44±4.28) pmol/L, (25.35±10.46) pmol/L, (6.62±2.41) nmol/L, and (182.44±50.47) nmol/L, and those in the hypothyroidism group were (4.86±1.33) mU/L, (5.16±1.44) pmol/L, (17.44±5.49) pmol/L, (2.25±0.46) nmol/L, and (121.44±50.72) nmol/L], with statistical differences (t=20.880, 13.035, 5.383, 14.450, and 6.758; all P<0.05). The relative expression of miRNA-192 in the hyperthyroidism group was lower than that in the hypothyroidism group [(0.34±0.11) vs. (0.92±0.45)], while the relative expression of miRNA-21 was higher than that in the hypothyroidism group [(0.61±0.23) vs. (0.22±0.07)], with statistical differences (t=9.720 and 13.128; both P<0.05). The Spearman correlation analysis showed that miRNA-192 was positively correlated with TSH and negatively with FT3, FT4, TT3, and TT4; miRNA-21 was negatively correlated with TSH and positively with FT3, FT4, TT3, and TT4. According to the ROC validation, the relative expression of miRNA-192 decreased, as the TSH decreased and the FT3, FT4, TT3, and TT4 increased; the relative expression of miRNA-21 increased, as the TSH decreased and the FT3, FT4, TT3, and TT4 increased. Conclusion　The relative expression of miRNA in peripheral blood is closely related to the changes of thyroid hormone levels, which has a high predictive effect for hyperthyroidism or hypothyroidism.

Key words:

Abnormal thyroid function, Thyroid hormone, Peripheral blood microRNAs, Correlation, Predictive performance

朱林青.

外周血微小RNA表达与甲状腺激素水平的关联及对甲状腺功能异常的预测效能分析 [J]. 国际医药卫生导报, 2023, 29(24): 3575-3579.

Zhu Linqing.

Correlation between expressions of microRNAs in peripheral blood and levels of thyroid hormones and its predictive effect on thyroid dysfunction [J]. International Medicine and Health Guidance News, 2023, 29(24): 3575-3579.

参考文献

[1] 王卫庆,沈力韵,刘建民,等. 新型冠状病毒肺炎疫情下甲状腺功能亢进症和甲状腺功能减退症管理专家建议[J]. 诊断学理论与实践,2022,21(2):128-129. DOI:10.16150/j.1671-2870.2022.02.003.
[2] 宋荣华,张进安. 青少年甲状腺疾病的特点和管理[J]. 中国实用内科杂志,2021,41(2):107-111. DOI:10.19538/j.nk2021020105.
[3] 中国医师协会中西医结合医师分会内分泌与代谢病学专业委员会. 甲状腺功能亢进症病证结合诊疗指南(2021-01-20)[J]. 世界中医药,2021,16(2):193-196. DOI:10.3969/j.issn.1673-7202.2021.02.003.
[4] 王久华,李晶.螺旋CT对甲状腺疾病的诊断及鉴别价值研究[J].中国地方病防治杂志,2022,37(3):264-265.
[5] 吕忠元,刘华,焦玉霞. 5000例妊娠妇女甲状腺激素水平分析及参考值建立[J]. 中国计划生育学杂志,2021,29(9):1983-1986. DOI:10.3969/j.issn.1004-8189.2021.09.046.
[6] 王洪涛,梁育岑,秦文科. 甲状腺功能亢进症患者外周血单个核细胞miR-206表达水平与Wnt/β-catenin通路相关性分析[J]. 中华地方病学杂志,2021,40(9):694-698. DOI:10.3760/cma.j.cn231583-20210406-00112.
[7] 中华医学会,中华医学会临床药学分会,中华医学会杂志社,等. 甲状腺功能亢进症基层合理用药指南[J]. 中华全科医师杂志,2021,20(5):515-519. DOI:10.3760/cma.j.cn114798-20210317-00249.
[8] 中华医学会,中华医学会临床药学分会,中华医学会杂志社,等. 甲状腺功能减退症基层合理用药指南[J]. 中华全科医师杂志,2021,20(5):520-522. DOI:10.3760/cma.j.cn114798-20210317-00250.
[9] Rovetta A. Raiders of the lost correlation: a guide on using pearson and spearman coefficients to detect hidden correlations in medical sciences [J]. Cureus, 2020, 12(11):e11794. DOI: 10.7759/cureus.11794.
[10] Wu Y. Nonparametric inference of the area under ROC curve under two-phase cluster sampling [J]. J Biopharm Stat, 2022, 32(2): 346-355. DOI: 10.1080/10543406. 2021.2009501.
[11] 周建,具紫勇,夏勇. 针刺联合甲巯咪唑片治疗甲状腺功能亢进症的临床疗效及对临床症状和甲状腺激素水平的影响[J]. 河北中医,2023,45(3):470-472. DOI:10.3969/j.issn.1002-2619.2023.03.026.
[12] 刘欢,陈鹏,李菲. 甲状腺功能减退对慢性肝病的影响[J]. 临床肝胆病杂志,2021,37(4):969-972. DOI:10.3969/j.issn.1001-5256.2021.04.054.
[13] 王伟伟,胡文华,许莹. 左甲状腺素钠在老年甲状腺功能减退综合征治疗中的应用[J]. 海南医学,2021,32(13):1662-1664. DOI:10.3969/j.issn.1003-6350.2021.13.009.
[14] 苗曦,王晓宇,马利双,等. 合肥市某区人群亚临床甲状腺功能减退症中促甲状腺激素水平与代谢综合征发病的相关性[J]. 安徽医科大学学报,2022,57(8):1318-1322. DOI:10.19405/j.cnki.issn1000-1492.2022.08.027.
[15] 王夕畅,单忠艳. 血清促甲状腺激素参考范围在诊断亚临床甲状腺功能减退症中的作用及其影响因素[J]. 中华内科杂志,2021,60(10):925-928. DOI:10.3760/cma.j.cn112138- 20210602-00391.
[16] 王夕畅,单忠艳. 血清促甲状腺激素参考范围在诊断亚临床甲状腺功能减退症中的作用及其影响因素[J]. 中华内科杂志,2021,60(10):925-928. DOI:10.3760/cma.j.cn112138- 20210602-00391.
[17] 张廷华,胡友元. MiRNA在甲状腺癌中的研究进展[J]. 生命的化学,2022,42(12):2231-2236. DOI:10.13488/j.smhx.20220531.
[18] Aranda A. MicroRNAs and thyroid hormone action []. Mol Cell Endocrinol, 2021, 525:111175. DOI: 10.1016/j.mce.2021.111175.
[19] Huang PS, Wang CS, Yeh CT, et al. Roles of thyroid hormone-associated microRNAs affecting oxidative stress in human hepatocellular carcinoma [J]. Int J Mol Sci, 2019, 20(20): 5220. DOI: 10.3390/ijms20205220.
[20] 丁莉,陈日秋,朱向盈,等. 甲状腺功能亢进患者外周血miRNA-21和miRNA-192的表达[J]. 广东医学,2022,43(2):213-216. DOI:10.13820/j.cnki.gdyx.20211393.