血清miR-19b、miR-744-5p水平在非小细胞肺癌诊断中的临床价值

doi:10.3760/cma.j.cn371439-20230308-00011

摘要/Abstract

摘要：

目的研究非小细胞肺癌（NSCLC）患者血清miR-19b、miR-744-5p水平，分析其在NSCLC诊断中的临床价值。方法选择吉林省肿瘤医院2019年8月至2022年8月收治的NSCLC患者226例（NSCLC组）和健康体检者100例（对照组）为研究对象。采用实时荧光定量PCR测定并比较NSCLC组和对照组血清miR-19b、miR-744-5p水平，分析二指标与NSCLC患者不同临床病理特征的关系，采用受试者操作特征曲线分析miR-19b、miR-744-5p和二者联合检测诊断NSCLC的临床价值。结果与对照组比较，NSCLC组血清miR-19b水平显著升高（3.86±1.25比1.06±0.41，t=21.87，P<0.001），miR-744-5p水平显著降低（1.80±0.48比5.75±1.69，t=32.36，P<0.001）。病理类型为腺癌、肿瘤最大径≥3 cm、中低分化、Ⅲ~Ⅳ期、伴有淋巴结转移的NSCLC患者血清miR-19b水平分别高于鳞状细胞癌（t=5.94，P<0.001）、肿瘤最大径<3 cm（t=2.65，P=0.009）、高分化（t=4.33，P<0.001）、Ⅰ~Ⅱ期（t=12.32，P<0.001）、不伴有淋巴结转移患者（t=8.13，P<0.001），而miR-744-5p水平分别低于鳞状细胞癌（t=8.27，P<0.001）、肿瘤最大径<3 cm（t=5.34，P<0.001）、高分化（t=6.95，P<0.001）、Ⅰ~Ⅱ期（t=11.40，P<0.001）、不伴有淋巴结转移患者（t=10.36，P<0.001）。血清miR-19b联合miR-744-5p检测诊断NSCLC的曲线下面积（AUC）为0.914（95%CI为0.841~0.959），敏感性和特异性分别为90.9%和84.0%，AUC显著大于miR-19b（AUC为0.824，95%CI为0.770~0.869）、miR-744-5p（AUC为0.783，95%CI为0.709~0.838）单一指标检测（Z=2.28，P=0.021；Z=2.36，P=0.017）。结论 NSCLC患者血清miR-19b水平升高、miR-744-5p水平降低，血清miR-19b、miR-744-5p联合检测在NSCLC诊断中具有较高的临床价值。

关键词: 癌, 非小细胞肺, miR-19b, miR-744-5p, 血清肿瘤标志物

Abstract:

Objective To investigate the serum levels of miR-19b and miR-744-5p in patients with non-small cell lung cancer （NSCLC），and to analyze the clinical value of miR-19b and miR-744-5p in the diagnosis of NSCLC. Methods A total of 226 NSCLC patients （NSCLC group）and 100 healthy people （control group）admitted to Jilin Cancer Hospital from August 2019 to August 2022 were selected as research objects. Quantitative real-time PCR was used to measure and compare the serum levels of miR-19b and miR-744-5p between the NSCLC group and the control group，and the relationships between the two indicators and different clinical and pathological characteristics of NSCLC patients were analyzed. The receiver operating characteristic curve was used to analyze the clinical value of miR-19b，miR-744-5p and their joint detection in the diagnosis of NSCLC. Results Compared with the control group，the serum miR-19b level （3.86±1.25 vs. 1.06±0.41）in the NSCLC group significantly increased （t=21.87，P<0.001），while the miR-744-5p level （1.80±0.48 vs. 5.75±1.69）significantly decreased （t=32.36，P<0.001）. The serum miR-19b levels in NSCLC patients with pathological types of adenocarcinoma，maximum tumor diameter ≥3 cm，medium to low differentiation，stage Ⅲ-Ⅳ，and with lymph node metastasis were higher than those in squamous cell carcinoma （t=5.94，P<0.001），maximum tumor diameter <3 cm （t=2.65，P=0.009），well differentiation （t=4.33，P<0.001），stageⅠ-Ⅱ （t=12.32，P<0.001），patients without lymph node metastasis （t=8.13，P<0.001），while miR-744-5p levels were lower than those in squamous cell carcinoma （t=8.27，P<0.001），tumor maximum diameter <3 cm （t=5.34，P<0.001），well differentiation （t=6.95，P<0.001），stageⅠ-Ⅱ （t=11.40，P<0.001），patients without lymph node metastasis （t=10.36，P<0.001）. The area under the curve （AUC）of serum miR-19b combined with miR-744-5p in the diagnosis of NSCLC was 0.914 （95%CI：0.841-0.959），with sensitivity and specificity of 90.9% and 84.0%，respectively. AUC was significantly than that of the single indicator detection of miR-19b （AUC=0.824，95%CI：0.770-0.869）and miR-744-5p （AUC=0.783，95%CI：0.709-0.838）（Z=2.28，P=0.021； Z=2.36，P=0.017）. Conclusion Serum miR-19b level of NSCLC patients is increased，miR-744-5p levels is decreased，and joint detection of serum miR-19b and miR-744-5p has high clinical value in the diagnosis of NSCLC.

Key words: Carcinoma, non-small-cell lung, miR-19b, miR-744-5p, Serum tumor markers

李丹, 李睿尧, 李膺函, 于秀艳, 吴雪峰. 血清miR-19b、miR-744-5p水平在非小细胞肺癌诊断中的临床价值[J]. 国际肿瘤学杂志, 2024, 51(2): 83-88.

Li Dan, Li Ruiyao, Li Yinghan, Yu Xiuyan, Wu Xuefeng. Clinical value of serum miR-19b and miR-744-5p levels in the diagnosis of non-small cell lung cancer[J]. Journal of International Oncology, 2024, 51(2): 83-88.

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参考文献 19

[1]	吴建辉, 储香玲, 王李强, 等. 中国肺癌患者真实世界免疫检查点抑制剂相关性肺炎的流行病学分析[J]. 中国癌症杂志, 2022, 32(6): 469-477. DOI: 10.19401/j.cnki.1007-3639.2022.06.001.
[2]	Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71(3): 209-249. DOI: 10.3322/caac.21660.
[3]	Zhu C, Zhuang W, Chen L, et al. Frontiers of ctDNA, targeted therapies, and immunotherapy in non-small-cell lung cancer[J]. Transl Lung Cancer Res, 2020, 9(1): 111-138. DOI: 10.21037/tlcr.2020.01.09.
[4]	Bade BC, Dela Cruz CS. Lung cancer 2020: epidemiology, etiology, and prevention[J]. Clin Chest Med, 2020, 41(1): 1-24. DOI: 10.1016/j.ccm.2019.10.001. pmid: 32008623
[5]	Ali Syeda Z, Langden SSS, Munkhzul C, et al. Regulatory mechanism of microRNA expression in cancer[J]. Int J Mol Sci, 2020, 21(5): 1723. DOI: 10.3390/ijms21051723.
[6]	王达, 马异峰, 马尚, 等. 血清miRNA-19b在早期非小细胞肺癌辅助诊断中的临床价值[J]. 临床肺科杂志, 2022, 27(8): 1172-1175. DOI: 10.3969/j.issn.1009-6663.2022.08.009.
[7]	Kleemann M, Schneider H, Unger K, et al. MiR-744-5p inducing cell death by directly targeting HNRNPC and NFIX in ovarian cancer cells[J]. Sci Rep, 2018, 8(1): 9020. DOI: 10.1038/s41598-018-27438-6. pmid: 29899543
[8]	Ren P, Chang L, Hong X, et al. Long non-coding RNA LINC01116 is activated by EGR1 and facilitates lung adenocarcinoma onco-genicity via targeting miR-744-5p/CDCA4 axis[J]. Cancer Cell Int, 2021, 21(1): 292. DOI: 10.1186/s12935-021-01994-w.
[9]	中华医学会, 中华医学会肿瘤学分会, 中华医学会杂志社. 中华医学会肺癌临床诊疗指南(2018版)[J]. 中华医学杂志, 2018, 40(12): 935-964. DOI: 10.3760/cma.j.issn.0253-3766.2018.12.012.
[10]	Weiland M, Gao XH, Zhou L, et al. Small RNAs have a large impact: circulating microRNAs as biomarkers for human diseases[J]. RNA Biol, 2012, 9(6): 850-859. DOI: 10.4161/rna.20378. pmid: 22699556
[11]	Liu R, Zhang YS, Zhang S, et al. MiR-126-3p suppresses the growth, migration and invasion of NSCLC via targeting CCR1[J]. Eur Rev Med Pharmacol Sci, 2019, 23(2): 679-689. DOI: 10.26355/eurrev_201901_16881.
[12]	高冰, 陈骏, 周欢, 等. 肺癌相关微小RNA表达水平及作用机制的研究进展[J]. 癌症进展, 2021, 19(3): 226-228. DOI: 10.11877/j.issn.1672-1535.2021.19.03.03.
[13]	陈国, 韩鹏黎, 陈柯茹, 等. miR-19b-3p靶向MTUS1调控甲状腺髓样癌细胞凋亡的分子机制[J]. 中国癌症杂志, 2021, 31(5): 390-396. DOI: 10.19401/j.cnki.1007-3639.2021.05.005.
[14]	王辉, 张潍, 张伟, 等. 非小细胞肺癌中miR-19a和miR-19b的表达及临床意义[J]. 现代肿瘤医学, 2015, 23(21): 3078-3081. DOI: 10.3969/j.issn.1672-4992.2015.21.009.
[15]	Thapa DR, Li X, Jamieson BD, et al. Overexpression of microRNAs from the miR-17-92 paralog clusters in AIDS-related non-Hodgkin's lymphomas[J]. PLoS One, 2011, 6(6): e20781. DOI: 10.1371/journal.pone.0020781.
[16]	Yu S, Yu H, Zhang Y, et al. Long non-coding RNA LINC01116 acts as an oncogene in prostate cancer cells through regulation of miR-744-5p/UBE2L3 axis[J]. Cancer Cell Int, 2021, 21(1): 168. DOI: 10.1186/s12935-021-01843-w. pmid: 33726770
[17]	李少鹏, 张鑫, 张涵, 等. 血清外泌体miR-744-5p在非小细胞肺癌中的表达水平及其临床意义[J]. 中华检验医学杂志, 2020, 43(2): 142-146. DOI: 10.3760/cma.j.issn.1009-9158.2020.02.008.
[18]	中华人民共和国卫生健康委员会. 原发性肺癌诊疗规范(2018年版)[J]. 肿瘤综合治疗电子杂志, 2019, 5(3): 100-120. DOI: 10.12151/JMCM.2019.03-16.
[19]	国家癌症中心, 国家肿瘤质控中心肺癌质控专家委员会. 中国原发性肺癌规范诊疗质量控制指标(2022版)[J]. 中华肿瘤杂志, 2022, 44(7): 594-599. DOI: 10.3760/cma.j.cn112152-20220418-00266.

基因	正向引物（5'-3'）	反向引物（5'-3'）
miR-19b	UGUGCAAAUCCAUGCAAAACUGA	GCTCACTGCAACCTCCTCCTCC
miR-744-5p	AAGGTGCGGGGCTAGGGCTAA	AGTAAGGTTGAGGTTA
U6	GCTTCGGCAGCACATATACTAAAT	CGCTTCACGAATTTGCGTGTACT

临床病理特征	例数		miR-19b		t值		P值	miR-744-5p		t值	P值
性别
男	139		4.14±1.33		1.95		0.052	5.88±1.76		1.40	0.163
女	87		3.79±1.28		1.95		0.052	5.54±1.80		1.40	0.163
年龄（岁）
≥60	154		4.14±1.39		1.73		0.086	5.93±1.79		1.90	0.059
<60	72		3.81±1.22		1.73		0.086	5.46±1.61		1.90	0.059
吸烟
是	57		4.11±1.35		1.74		0.083	5.98±1.82		1.79	0.075
否	169		3.76±1.30		1.74		0.083	5.51±1.68		1.79	0.075
肿瘤位置
右肺	128		3.92±1.22		0.81		0.422	5.82±1.67		0.88	0.381
左肺	98		3.79±1.18		0.81		0.422	5.62±1.73		0.88	0.381
病理类型
腺癌	141	4.52±1.34		5.94		<0.001		4.82±1.56	8.27		<0.001
鳞状细胞癌	85	3.48±1.16		5.94		<0.001		6.67±1.74	8.27		<0.001
肿瘤最大径（cm）
<3	144	3.56±1.09		2.65		0.009		6.36±1.62	5.34		<0.001
≥3	82	3.98±1.24		2.65		0.009		5.15±1.67	5.34		<0.001
分化程度
中低分化	136	4.23±1.35		4.33		<0.001		4.98±1.52	6.95		<0.001
高分化	90	3.46±1.13		4.33		<0.001		6.54±1.73	6.95		<0.001
TNM分期
Ⅰ~Ⅱ期	155	2.83±1.04		12.32		<0.001		7.35±2.08	11.40		<0.001
Ⅲ~Ⅳ期	71	4.96±1.51		12.32		<0.001		4.29±1.31	11.40		<0.001
淋巴转移
有	68	4.64±1.34		8.13		<0.001		4.48±1.33	10.36		<0.001
无	158	3.26±1.09		8.13		<0.001		7.27±2.04	10.36		<0.001