Diagnostic value of miR-124a and miR-449a in plasma of non-small cell lung cancer

doi:10.3969/j.issn.1673-8640.2021.01.007

Abstract

Abstract:

Objective To explore the diagnostic value of microRNA-124a（miR-124a）and microRNA-449a（miR-449a） in non-small cell lung cancer（NSCLC）. Methods Ninety patients with NSCLC who underwent surgical resection and were followed up for 36 months were assigned to NSCLC group and subdivided into relapsed group（56 cases）and non-relapsed group（34 cases）. In addition,60 patients with benign lung nodules（benign nodules group） and 80 healthy persons（normal control group） were enrolled in this study. General information of all the subjects was collected. Serum neuron specific enolase（NSE）,miR-124a and miR-449a levels were detected. Spearman correlation analysis was applied to evaluate the relevance of indicators. The receiver operating characteristic（ROC） curve was used to evaluate the effectiveness of the indicators in the diagnosis of NSCLC. Results Compared with those in the normal control group and benign nodule group, serum NSE was significantly increased in the NSCLC group （P<0.05）,but the serum levels of miR-124a and miR-449a were significantly decreased（P<0.05）. There was no statistically significant difference in serum levels of NSE,miR-124a or miR-449a between the normal control group and benign nodule group（P>0.05）. Compared with those in the non-relapsed group,serum NSE of the relapsed group increased（P<0.05）,while the levels of miR-124a and miR-449a decreased（P<0.05）. There was no significant difference in age,gender,body mass index（BMI）,smoking status,tumor diameter,pathological type and TNM stage between the two groups（P>0.05）. ROC curve analysis results showed that the area under curve（AUC）of NSE,miR-124a and miR-449a for single diagnosis of NSCLC were 0.660,0.703 and 0.759,respectively. The combined detection of NSE+miR-124a+miR-449a had the highest AUC（0.895） and sensitivity（96.25%） for the diagnosis of NSCLC. The combined detection of miR-124a+miR-449a had the highest specificity（90.31%） for the diagnosis of NSCLC. Conclusion miR-124a and miR-449a may be used as auxiliary diagnostic indicators for NSCLC.

Key words: MicroRNA-124a, MicroRNA-449a, Neuron specific enolase, Non-small cell lung cancer

CLC Number:

R393

PENG Jiaowu, SUN Chengmou. Diagnostic value of miR-124a and miR-449a in plasma of non-small cell lung cancer[J]. Laboratory Medicine, 2021, 36(1): 34-38.

Figures/Tables 4

References 19

[1]	殷金兰,李莹,陈金梅,等. 4项肿瘤标志物检测在晚期非小细胞肺癌治疗中的意义[J]. 国际检验医学杂志,2017,38(14):1985-1987.
[2]	许子寒,郑林鹏,杨峤,等. 非小细胞肺癌的转移特征及预后分析[J]. 第三军医大学学报,2019,41(9):871-876.
[3]	ZHANG E,XU Z,DUAN W,et al.Association between polymorphisms in pre-miRNA genes and risk of oral squamous cell cancer in a Chinese population[J]. PLoS One,2017,12(6):e0176044.
[4]	崔胜金,曹朝鹏,郭伟权,等. 非小细胞肺癌早期诊断的潜在生物标志物:血浆miRNA-23a和miRNA-451[J]. 南方医科大学学报,2019,39(6):705-711.
[5]	GUO W,ZHANG Y,ZHANG Y,et al.Decreased expression of miR-204 in plasma is associated with a poor prognosis in patients with non-small cell lung cancer[J]. Int J Mol Med,2015,36(6):1720-1726.
[6]	YU F,LIU J B,WU Z J,et al.Tumor suppressive microRNA-124a inhibits stemness and enhances gefitinib sensitivity of non-small cell lung cancer cells by targeting ubiquitin-specific protease 14[J]. Cancer Lett,2018,427:74-84.
[7]	HE Y M,JI A J,XU X Y,et al.miR-449a:a potential therapeutic agent for cancer[J]. Anticancer Drugs,2017,28(10):1067-1078.
[8]	袁双虎,于金明. 《原发性肺癌诊疗规范(2015年版)》放射治疗更新解读[J]. 中国医师杂志,2016,18(6):801-804.
[9]	FERNANDES S L,GURUPUR V P,LIN H,et al.A novel fusion approach for early lung cancer detection using computer aided diagnosis techniques[J]. J Med Imaging Health Inf,2017,7(8):1841-1850.
[10]	SHANG X,ZI H,LI Y,et al.Combined use of salivary biomarkers and carcinoembryonic antigen for lung cancer detection in a Chinese population[J]. Medicine(Baltimore),2019,98(31):e16511.
[11]	WONG N W,CHEN Y,CHEN S,et al.OncomiR:an online resource for exploring pan-cancer microRNA dysregulation[J]. Bioinformatics,2018,34(4):713-715.
[12]	NIXON A M,PROVATOPOULOU X,KALOGERA E,et al.Circulating thyroid cancer biomarkers:current limitations and future prospects[J]. Clin Endocrinol(Oxf),2017,87(2):117-126.
[13]	YOU Z,HUANG Z A,ZHU Z X,et al.PBMDA:a novel and effective path-based computational model for miRNA-disease association prediction[J]. PLoS Comput Biol,2017,13(3):e1005455.
[14]	LANG F M,HOSSAIN A,GUMIN J,et al.Mesenchymal stem cells as natural bio-factories for exosomes carrying miR-124a in the treatment of gliomas[J]. Neuro Oncol,2018,20(3):380-390.
[15]	DENG N,LI L,GAO J,et al.Hsa_circ_0009910 promotes carcinogenesis by promoting the expression of miR-449a target IL6R in osteosarcoma[J]. Biochem Biophys Res Commun,2018,495(1):189-196.
[16]	SUN X,LIU S,CHEN P,et al.miR-449a inhibits colorectal cancer progression by targeting SATB2[J]. Oncotarget,2016,8(60):100975-100988.
[17]	邓雪松,潘红艳,成俊,等. 上调miR-449a表达对肝癌细胞生长和侵袭能力的影响[J]. 中国普通外科杂志,2018,27(1):68-74.
[18]	SHINTANI T,MATSUO Y,IIZUKA Y,et al.Prognostic significance of serum nse for non-small cell lung cancer patients receiving stereotactic body radiotherapy[J]. Anticancer Res,2017,37(9):5161-5167.
[19]	BARNETT D,LIU Y,PARTYKA K,et al.Abstract 1754:a new glycan biomarker for pancreatic cancer complements CA19-9 and identifies a distinct subpopulation of cancer cells[J]. Cancer Res,2017,77(13):1754.

组别	例数	年龄/岁	性别		BMI/（kg/m²）	吸烟史
组别	例数	年龄/岁	男/例	女/例	BMI/（kg/m²）	有/例	无/例
NSCLC组	90	67.89±8.16	62	28	22.54±1.59	68	22
良性结节组	60	66.92±12.54	37	23	21.58±2.17	42	18
正常对照组	80	66.18±10.28	52	28	22.95±2.01	51	29
统计值		1.207	0.290		1.483	2.811
P值		0.229	0.590		0.140	0.094
组别	Hb/（g/L）		NSE/（ng/mL）		miR-124a	miR-449a
NSCLC组	115.49±21.28		28.26±3.54		0.52±0.04	0.76±0.07
良性结节组	117.28±16.48		2.37±0.94		0.96±0.12	1.05±0.09
正常对照组	118.24±15.31		2.31±0.42		1.00±0.06	1.00±0.05
统计值	0.957		40.037		61.976	25.433
P值	0.340		0.000		0.000	0.000

组别	例数	年龄/岁	性别		BMI/（kg/m²）	吸烟史
组别	例数	年龄/岁	男/例	女/例	BMI/（kg/m²）	有/例	无/例
NSCLC组	90	67.89±8.16	62	28	22.54±1.59	68	22
良性结节组	60	66.92±12.54	37	23	21.58±2.17	42	18
正常对照组	80	66.18±10.28	52	28	22.95±2.01	51	29
统计值		1.207	0.290		1.483	2.811
P值		0.229	0.590		0.140	0.094
组别	Hb/（g/L）		NSE/（ng/mL）		miR-124a	miR-449a
NSCLC组	115.49±21.28		28.26±3.54		0.52±0.04	0.76±0.07
良性结节组	117.28±16.48		2.37±0.94		0.96±0.12	1.05±0.09
正常对照组	118.24±15.31		2.31±0.42		1.00±0.06	1.00±0.05
统计值	0.957		40.037		61.976	25.433
P值	0.340		0.000		0.000	0.000

组别	例数	年龄/岁	性别		BMI/ （kg/m²）	吸烟史		肿瘤直径
组别	例数	年龄/岁	男/例	女/例	BMI/ （kg/m²）	有/例	无/例	<5 cm/例	≥5 cm/例
未复发组	34	66.26±5.94	23	11	22.97±1.67	27	7	13	21
复发组	56	68.15±9.05	39	17	22.20±1.86	41	15	20	36
统计值		1.083	0.039		1.977	0.440		0.058
P值		0.282	0.843		0.051	0.507		0.810
组别	病理类型		TNM分期		NSE/ （ng/mL）	miR-124a		miR-449a
组别	鳞癌/例	腺癌/例	Ⅰ~Ⅱ期/例	Ⅲ期/例	NSE/ （ng/mL）	miR-124a		miR-449a
未复发组	17	17	13	21	8.64±2.73	0.67±0.09		0.75±0.05
复发组	29	27	23	33	29.16±4.52	0.36±0.08		0.53±0.04
统计值	0.027		0.071		26.851	16.997		22.989
P值	0.869		0.790		0.000	0.000		0.000

组别	例数	年龄/岁	性别		BMI/ （kg/m²）	吸烟史		肿瘤直径
组别	例数	年龄/岁	男/例	女/例	BMI/ （kg/m²）	有/例	无/例	<5 cm/例	≥5 cm/例
未复发组	34	66.26±5.94	23	11	22.97±1.67	27	7	13	21
复发组	56	68.15±9.05	39	17	22.20±1.86	41	15	20	36
统计值		1.083	0.039		1.977	0.440		0.058
P值		0.282	0.843		0.051	0.507		0.810
组别	病理类型		TNM分期		NSE/ （ng/mL）	miR-124a		miR-449a
组别	鳞癌/例	腺癌/例	Ⅰ~Ⅱ期/例	Ⅲ期/例	NSE/ （ng/mL）	miR-124a		miR-449a
未复发组	17	17	13	21	8.64±2.73	0.67±0.09		0.75±0.05
复发组	29	27	23	33	29.16±4.52	0.36±0.08		0.53±0.04
统计值	0.027		0.071		26.851	16.997		22.989
P值	0.869		0.790		0.000	0.000		0.000

指标	AUC（95%可信区间）	最佳临界值	P值	敏感性/%	特异性/%
NSE	0.660（0.582~0.737）	20.39 ng/mL	0.000	82.61	44.72
miR-124a	0.703（0.628~0.778）	0.48	0.004	81.46	55.37
miR-449a	0.759（0.690~0.828）	0.62	0.000	72.16	73.26
NSE+miR-124a	0.749（0.679~0.771）		0.000	58.14	83.56
NSE+miR-449a	0.792（0.726~0.857）		0.000	68.63	81.69
miR-124a+miR-449a	0.828（0.769~0.887）		0.001	64.59	90.31
NSE+miR-124a+miR-449a	0.895（0.821~0.967）		0.000	96.25	55.02