miR-21、miR-222、miR-146b和miR-7检测在甲状腺乳头状癌诊断中的价值

doi:10.3969/j.issn.1673-8640.2024.11.001

摘要/Abstract

摘要：

目的探讨miR-21、miR-222、miR-146b和miR-7在甲状腺乳头状癌（PTC）诊断中的价值。方法选取2020年12月—2021年12月云南省第三人民医院PTC患者150例（PTC组）、甲状腺良性结节患者50例（良性结节组）和健康体检者50名（正常对照组）。收集所有研究对象的临床资料，并检测miR-21、miR-222、miR-146b和miR-7。采用受试者工作特征（ROC）曲线评估各项指标鉴别诊断良性结节与PTC的效能。结果 PTC组、良性结节组和正常对照组血浆miR-21、miR-146b、miR-222相对表达量依次降低（P<0.001），血浆miR-7相对表达量依次升高（P<0.001）。不同肿瘤分期的PTC患者之间血浆miR-222相对表达量差异有统计学意义（P<0.05）。有无淋巴转移的PTC患者之间血浆miR-146b相对表达量差异有统计学意义（P<0.05）。不同性别、年龄、肿块大小、肿瘤分期和有无淋巴转移的PTC患者之间血浆miR-21和miR-7相对表达量差异均无统计学意义（P>0.05）。miR-21、miR-146b、miR-222和miR-7单项检测鉴别诊断PTC与良性结节的曲线下面积（AUC）分别为 0.743、0.828、0.708、0.777。4项指标联合检测的AUC（0.933）除与miR-222＋miR-146b＋miR-7组合（0.917）差异无统计学意义（P>0.05）外，均高于其他任意3项组合、2项组合和单项检测的AUC（P<0.05）。miR-222＋miR-146b＋miR-7和4种miRNA联合检测鉴别诊断早期（Ⅰ~Ⅱ期）PTC和良性结节的AUC分别为0.914、0.925，差异无统计学意义（P>0.05）；鉴别诊断中晚期（Ⅲ~Ⅳ期）PTC和良性结节的AUC分别为0.938、0.992，差异无统计学意义（P>0.05）。结论 miR-146b和miR-222与PTC的病情相关。miR-222、miR-146b、miR-7联合检测鉴别诊断良性、恶性甲状腺结节和不同分期PTC的效能均较高，具有临床推广价值。

关键词: miR-21, miR-146b, miR-222, miR-7, 乳头状甲状腺癌

Abstract:

Objective To investigate the diagnostic roles of miR-21，miR-222，miR-146b and miR-7 for papillary thyroid carcinoma （PTC）. Methods From December 2020 to December 2021，150 patients with PTC（PTC group），50 patients with benign thyroid nodules （benign nodule group） and 50 healthy subjects（healthy control group）were enrolled from the Third People's Hospital of Yunnan Province. All the clinical data of the research subjects were collected，and miR-21，miR-222，miR-146b and miR-7 were determined. The efficacy of each index in diagnosing PTC was evaluated by receiver operating characteristic（ROC）curve. Results The relative expression levels of miR-21，miR-222 and miR-146b in PTC group，benign nodule group and healthy control group were decreased successively （P<0.001），while the relative expression level of miR-7 was increased successively （P<0.001）. There was statistical significance in the relative expression level of miR-222 among patients with different tumor stages（P<0.05）. The relative expression level of miR-146b differed between patients with and without lymphatic metastasis （P<0.05）. The relative expression levels of miR-21 and miR-7 were not statistically significant among patients with different genders，ages，tumor sizes， tumor stages and lymphatic metastasis（P>0.05）.The areas under curves（AUC） of miR-21，miR-222，miR-146b and miR-7 single determinations in the differential diagnosis of PTC and benign nodules were 0.743，0.828，0.708 and 0.777，respectively. The AUC （0.933） of the combined determination of the 4 indicators was higher than those of the other three-three combinations，except for miR-222+miR-146b+miR-7 （0.917）（P>0.05），and it was also higher than those of the other two-two combinations and single determinations （P<0.05）. The AUC of miR-222+miR-146b+miR-7 and the combined determination of the 4 indicators for the differential diagnosis of early （stage Ⅰ-Ⅱ） PTC and benign nodules were 0.914 and 0.925，respectively （P>0.05）. For the differential diagnosis of middle-late （stage Ⅲ-Ⅳ） PTC and benign nodules，the AUC were 0.938 and 0.992，respectively （P>0.05）. Conclusions MiR-146b and miR-222 are associated with the condition of PTC. The combined determination of miR-222，miR-146b and miR-7 has a relatively high efficacy in differentiating benign and malignant thyroid nodules in both the early and advanced stages of thyroid carcinoma.

Key words: MiR-21, MiR-146b, MiR-222, MiR-7, Papillary thyroid carcinoma

中图分类号:

R446.7

梁良, 杨海清, 李亚山, 汪坚, 满宝华, 唐海先, 张晓珺, 何赛, 殷燕. miR-21、miR-222、miR-146b和miR-7检测在甲状腺乳头状癌诊断中的价值[J]. 检验医学, 2024, 39(11): 1027-1034.

LIANG Liang, YANG Haiqing, LI Yashan, WANG Jian, MAN Baohua, TANG Haixian, ZHANG Xiaojun, HE Sai, YIN Yan. Clinical roles of miR-21，miR-222，miR-146b and miR-7 in diagnosis of papillary thyroid carcinoma[J]. Laboratory Medicine, 2024, 39(11): 1027-1034.

图/表 8

参考文献 21

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基因名称	上游引物（5'~3'）	下游引物^①
miR-21	UAGCUUAUCAGACUGAUGUUGA	通用引物
miR-146b	UGAGAACUGAAUUCCAUAGGCU	通用引物
miR-222	CUCAGUAGCCAGUGUAGAUCCU	通用引物
miR-7	UGGAAGACUAGUGAUUUUGUUGU	通用引物
U6	GGAACGATACAGAGAAGATTAGC	通用引物

基因名称	上游引物（5'~3'）	下游引物^①
miR-21	UAGCUUAUCAGACUGAUGUUGA	通用引物
miR-146b	UGAGAACUGAAUUCCAUAGGCU	通用引物
miR-222	CUCAGUAGCCAGUGUAGAUCCU	通用引物
miR-7	UGGAAGACUAGUGAUUUUGUUGU	通用引物
U6	GGAACGATACAGAGAAGATTAGC	通用引物

组别	例数	miR-21	miR-146b	miR-222	miR-7
正常对照组	50	1.06±0.48	1.09±0.40	1.05±0.34	1.09±0.49
良性结节组	50	2.25±1.40*	1.96±0.46*	2.49±0.59*	0.63±0.23*
PTC 组	150	4.12±3.13*#	2.97±1.12*#	4.06±2.38*#	0.39±0.22*#
F值		31.53	86.30	52.04	107.63
P值		<0.001	<0.001	<0.001	<0.001

组别	例数	miR-21	miR-146b	miR-222	miR-7
正常对照组	50	1.06±0.48	1.09±0.40	1.05±0.34	1.09±0.49
良性结节组	50	2.25±1.40*	1.96±0.46*	2.49±0.59*	0.63±0.23*
PTC 组	150	4.12±3.13*#	2.97±1.12*#	4.06±2.38*#	0.39±0.22*#
F值		31.53	86.30	52.04	107.63
P值		<0.001	<0.001	<0.001	<0.001

项目	例数	miR-21	miR-146b	miR-222	miR-7
性别
男	50	4.53±3.95	3.05±1.22	4.14±2.23	0.39±0.23
女	100	3.92±2.63	2.93±1.08	4.02±2.47	0.39±0.21
t值		1.110	0.615	0.309	-0.029
P值		0.269	0.540	0.758	0.977
年龄
≥45岁	69	4.47±3.78	3.00±1.08	4.18±2.52	0.39±0.21
<45岁	81	3.83±2.43	2.94±1.17	3.95±2.28	0.38±0.24
t值		-1.218	-0.332	-0.572	-0.339
P值		0.226	0.740	0.568	0.735
肿块大小
≥1 cm	34	4.40±2.90	3.21±1.47	4.59±2.42	0.38±0.21
<1 cm	116	4.04±3.21	2.90±0.99	3.90±2.36	0.39±0.22
t值		-0.587	-1.151	-1.499	-0.140
P值		0.558	0.256	0.136	0.889
淋巴转移
有	29	5.12±4.61	3.54±0.99	4.66±3.00	0.42±0.25
无	121	3.89±2.63	2.84±1.45	3.91±2.00	0.38±0.21
t值		-1.282	-2.485	-1.664	-1.060
P值		0.176	0.018	0.216	0.291
肿瘤分期
Ⅰ~Ⅱ期	130	3.97±3.15	2.87±0.98	3.87±2.28	0.39±0.22
Ⅲ~Ⅳ期	20	5.11±2.92	3.62±1.70	5.31±2.73	0.34±0.20
t值		-1.510	-1.931	-2.574	0.929
P值		0.133	0.067	0.011	0.324