血清miR-106b-5p、miR-760联合低剂量螺旋CT诊断早期肺癌的临床价值

doi:10.3760/cma.j.cn371439-20240215-00055

摘要/Abstract

摘要：

目的探讨微RNA（miR）-106b-5p、miR-760在早期肺癌患者血清中的水平以及联合低剂量螺旋CT在诊断早期肺癌中的临床价值。方法收集2022年1月至2023年3月于河北省沧州市人民医院进行治疗的90例早期肺癌患者（肺癌组）作为研究对象，同时选取同期90例经病理确诊为肺部良性病变（良性肺结节）的患者作为对照组。比较两组患者血清miR-106b-5p、miR-760水平，对低剂量螺旋CT检查结果进行分析；绘制受试者操作特征曲线，确定血清miR-106b-5p、miR-760的最佳截断值；四格表分析血清miR-106b-5p、miR-760联合低剂量螺旋CT对早期肺癌的诊断效能。结果肺癌组患者血清miR-106b-5p水平高于对照组（1.39±0.31比1.04±0.30），血清miR-760水平低于对照组（0.75±0.24比1.02±0.26），差异均有统计学意义（t=7.70，P<0.001；t=7.24，P<0.001）。miR-106b-5p、miR-760、低剂量螺旋CT诊断早期肺癌的曲线下面积（AUC）分别为0.83、0.81、0.82，准确率分别为76.67%、77.22%、81.67%，敏感性分别为84.44%、81.11%、76.67%，特异性分别为68.89%、73.33%、86.67%。血清miR-106b-5p、miR-760联合低剂量螺旋CT诊断早期肺癌的AUC为0.96，准确率为90.00%，敏感性为94.44%，特异性为85.56%。三项联合诊断的准确率高于miR-106b-5p、miR-760、低剂量螺旋CT单独诊断（χ²=11.52，P=0.001；χ²=10.72，P=0.001；χ²=5.14，P=0.023）；三项联合诊断的敏感性高于miR-106b-5p、miR-760、低剂量螺旋CT单独诊断（χ²=4.77，P=0.029；χ²=7.46，P=0.006；χ²=11.51，P=0.001）；三项联合诊断的特异性高于miR-106b-5p、miR-760单独诊断（χ²=7.11，P=0.008；χ²=4.12，P=0.042）。结论早期肺癌患者血清miR-106b-5p水平显著升高，miR-760水平显著降低，miR-106b-5p、miR-760联合低剂量螺旋CT对早期肺癌具有较高的诊断价值。

关键词: 肺肿瘤, 诊断, 微RNA-106b-5p, 微RNA-760, 低剂量螺旋CT

Abstract:

Objective To investigate the levels of microRNA （miR）-106b-5p and miR-760 in the serum of early lung cancer patients， and the clinical value of the combination of them and low-dose spiral CT in the diagnosis of early lung cancer. Methods Ninety early lung cancer patients （lung cancer group） who underwent treatment in Cangzhou People's Hospital of Hebei Province from January 2022 to March 2023 were collected as research subjects， meantime， 90 patients with benign pulmonary lesions （benign pulmonary nodules） diagnosed by pathology were selected as the control group. The levels of miR-106b-5p and miR-760 in the serum of two groups were compared， the results of low-dose spiral CT examination were analyzed； receiver operating characteristic curve was drawn to determine the optimal cut-off values of serum miR-106b-5p and miR-760； four grid table method was applied to analyze the diagnostic efficacy of serum miR-106b-5p， miR-760 combined with low-dose spiral CT for early lung cancer. Results The level of miR-106b-5p in lung cancer group was higher than that in control group （1.39±0.31 vs. 1.04±0.30）， serum miR-760 level was lower than that in control group （0.75±0.24 vs. 1.02±0.26）， with statistically significant differences （t=7.70， P<0.001； t=7.24， P<0.001）. The area under curve （AUC） of miR-106b-5p， miR-760 and low-dose spiral CT in the diagnosis of early lung cancer was 0.83， 0.81 and 0.82， the accuracy was 76.67%， 77.22% and 81.67%， the sensitivity was 84.44%， 81.11% and 76.67%， and the specificity was 68.89%， 73.33% and 86.67%， respectively. The AUC， accuracy， sensitivity， and specificity of serum miR-106b-5p， miR-760 combined with low-dose spiral CT in diagnosing early lung cancer were 0.96， 90.00%， 94.44%， and 85.56%， respectively. The accuracy of the three combined diagnosis was higher than that of individual diagnosis of miR-106b-5p， miR-760 and low-dose spiral CT （χ²=11.52， P=0.001； χ²=10.72， P=0.001； χ²=5.14， P=0.023）， the sensitivity of the three combined diagnosis was higher than that of individual diagnosis of miR-106b-5p， miR-760 and low-dose spiral CT （χ²=4.77， P=0.029； χ²=7.46，P=0.006； χ²=11.51， P=0.001）， the specificity of the three combined diagnosis was higher than that of individual diagnosis of miR-106b-5p， miR-760 （χ²=7.11， P=0.008； χ²=4.12， P=0.042）. Conclusion The serum level of miR-106b-5p is significantly increased in early lung cancer patients， while the serum level of miR-760 is significantly reduced. The combination of miR-106b-5p， miR-760 and low-dose spiral CT has high diagnostic value for early lung cancer.

Key words: Lung neoplasms, Diagnosis, MicroRNA-106b-5p, MicroRNA-760, Low-dose spiral CT

刘娜, 寇介丽, 杨枫, 刘桃桃, 李丹萍, 韩君蕊, 杨立洲. 血清miR-106b-5p、miR-760联合低剂量螺旋CT诊断早期肺癌的临床价值[J]. 国际肿瘤学杂志, 2024, 51(6): 321-325.

Liu Na, Kou Jieli, Yang Feng, Liu Taotao, Li Danping, Han Junrui, Yang Lizhou. Clinical value of serum miR-106b-5p and miR-760 combined with low-dose spiral CT in the diagnosis of early lung cancer[J]. Journal of International Oncology, 2024, 51(6): 321-325.

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参考文献 20

[1]	Wéber A, Morgan E, Vignat J, et al. Lung cancer mortality in the wake of the changing smoking epidemic: a descriptive study of the global burden in 2020 and 2040[J]. BMJ Open, 2023, 13(5): e065303. DOI: 10.1136/bmjopen-2022-065303.
[2]	Ning J, Ge T, Jiang ML, et al. Early diagnosis of lung cancer: which is the optimal choice?[J]. Aging (Albany NY), 2021, 13(4): 6214-6227. DOI: 10.18632/aging.202504.
[3]	Chen M, Copley SJ, Viola P, et al. Radiomics and artificial intelligence for precision medicine in lung cancer treatment[J]. Semin Cancer Biol, 2023, 93: 97-113. DOI: 10.1016/j.semcancer.2023.05.004. pmid: 37211292
[4]	Zhou LY, Wang W, Wang FF, et al. Plasma-derived exosomal miR-15a-5p as a promising diagnostic biomarker for early detection of endometrial carcinoma[J]. Mol Cancer, 2021, 20(1): 57. DOI: 10.1186/s12943-021-01352-4. pmid: 33781255
[5]	Wang Z, Li TE, Chen M, et al. MiR-106b-5p contributes to the lung metastasis of breast cancer via targeting CNN1 and regulating Rho/ROCK1 pathway[J]. Aging (Albany NY), 2020, 12(2): 1867-1887. DOI: 10.18632/aging.102719.
[6]	Zhu YC, Zhang C, Jiang B, et al. MiR-760 targets HBEGF to control cartilage extracellular matrix degradation in osteoarthritis[J]. J Orthop Surg Res, 2023, 18(1): 186. DOI: 10.1186/s13018-023-03664-1. pmid: 36894989
[7]	Yu WL, Wang L, Liu S, et al. Combination of serum ACSL4 levels and low-dose 256-slice spiral CT exhibits the potential in the early screening of lung cancer[J]. Medicine (Baltimore), 2023, 102(5): e32733. DOI: 10.1097/MD.0000000000032733.
[8]	Zheng YJ, Fang ZY, Xue Y, et al. Specific gut microbiome signature predicts the early-stage lung cancer[J]. Gut Microbes, 2020, 11(4): 1030-1042. DOI: 10.1080/19490976.2020.1737487. pmid: 32240032
[9]	Wang YZ, Lv YB, Li GY, et al. Value of low-dose spiral CT combined with circulating miR-200b and miR-200c examinations for lung cancer screening in physical examination population[J]. Eur Rev Med Pharmacol Sci, 2021, 25(19): 6123-6130. DOI: 10.26355/eurrev_202110_26890.
[10]	Xu KH, Zhang CP, Du TT, et al. Progress of exosomes in the diagnosis and treatment of lung cancer[J]. Biomed Pharmacother, 2021, 134: 111111. DOI: 10.1016/j.biopha.2020.111111. pmid: 33352449
[11]	Farré PL, Duca RB, Massillo C, et al. MiR-106b-5p: a master regulator of potential biomarkers for breast cancer aggressiveness and prognosis[J]. Int J Mol Sci, 2021, 22(20): 11135. DOI: 10.3390/ijms222011135.
[12]	Shi Y, Zhang B, Zhu J, et al. MiR-106b-5p inhibits IRF1/IFN-β signaling to promote M2 macrophage polarization of glioblastoma[J]. Onco Targets Ther, 2020, 13: 7479-7492. DOI: 10.2147/OTT.S238975.
[13]	Yang F, Sun ZW, Wang DY, et al. MiR-106b-5p regulates eso-phageal squamous cell carcinoma progression by binding to HPGD[J]. BMC Cancer, 2022, 22(1): 308. DOI: 10.1186/s12885-022-09404-8. pmid: 35317779
[14]	Yong WM, Deng SJ, Tan YF, et al. Circular RNA circSLC8A1 inhibits the proliferation and invasion of non-small cell lung cancer cells through targeting the miR-106b-5p /FOXJ3 axis[J]. Cell Cycle, 2021, 20(24): 2597-2606. DOI: 10.1080/15384101.2021.1995968.
[15]	Yang YZ, Zhang YF, Yang L, et al. MiR‑760 mediates hypoxia-induced proliferation and apoptosis of human pulmonary artery smooth muscle cells via targeting TLR4[J]. Int J Mol Med, 2018, 42(5): 2437-2446. DOI: 10.3892/ijmm.2018.3862.
[16]	Wang S, Yang Y, Cao YD, et al. Androgen downregulation of miR-760 promotes prostate cancer cell growth by regulating IL6[J]. Asian J Androl, 2021, 23(1): 85-90. DOI: 10.4103/aja.aja_20_20.
[17]	Wu XD, Chen H, Liu N, et al. Curcumin suppresses lung cancer progression via circRUNX1 mediated miR-760/RAB3D axis[J]. Thorac Cancer, 2023, 14(5): 506-516. DOI: 10.1111/1759-7714.14773.
[18]	Wang W, He B. MiR-760 inhibits the progression of non-small cell lung cancer through blocking ROS1/Ras/Raf/MEK/ERK pathway[J]. Biosci Rep, 2020, 30: BSR20182483. DOI: 10.1042/BSR 20182483.
[19]	El-Aal AEA, Elshafei A, Ismail MY, et al. Identification of miR-106b-5p, miR-601, and miR-760 expression and their clinical values in non-small cell lung cancer (NSCLC) patients' serum[J]. Pathol Res Pract, 2023, 248: 154663. DOI: 10.1016/j.prp.2023.154663.
[20]	Zheng CQ, Wang HF, Liu QZ, et al. Application effect of low-dose spiral CT on pulmonary nodules and its diagnostic value for benign and malignant nodules[J]. Am J Transl Res, 2023, 15(1): 256-263. pmid: 36777849

基因	正向引物	反向引物
miR-106b-5p	5’-ATGCTATCTCATACGTGTCA-3’	5’-GATCCATAGTCGATCTGGAT-3’
miR-760	5’-TATTGCTTAAGAATACGCGTAG-3’	5’-AACTCCAGCAGGACCATGTGAT-3’
U6	5’-GACCTCTATGCCAACACAGT-3’	5’-AGTACTTGCGCTCAGGAGGA-3’

一般临床资料	对照组（n=90）	肺癌组（n=90）	t/χ²值	P值
年龄（岁）	55.28±6.74	56.73±6.85	1.43	0.154
性别
男	53（58.89）	57（63.33）	0.37	0.541
女	37（41.11）	33（36.67）	0.37	0.541
BMI（kg/m²）	22.47±3.25	21.89±3.47	1.16	0.249
吸烟史
无	62（68.89）	57（63.33）	0.62	0.431
有	28（31.11）	33（36.67）	0.62	0.431
饮酒史
无	59（65.56）	51（56.67）	1.50	0.221
有	31（34.44）	39（43.33）	1.50	0.221
结节直径（mm）	14.58±3.96	19.76±4.03	8.70	<0.001
病理类型
NSCLC	-	74（82.22）	-	-
SCLC	-	16（17.78）	-	-

低剂量螺旋 CT检查	病理结果		合计
低剂量螺旋 CT检查	阳性	阴性	合计
阳性	69	12	81
阴性	21	78	99
合计	90	90	180