血清外泌体miR-205-5p/miR-152-5p对早期非小细胞肺癌的诊断价值

doi:10.6040/j.issn.1671-7554.0.2019.455

摘要/Abstract

摘要： 目的探索血清外泌体miR-205-5p/miR-152-5p联合相对表达量在早期非小细胞肺癌(NSCLC)患者血清中的水平及诊断价值。方法纳入TNM分期为0-II期的NSCLC患者(NSCLC组)83例(包括腺癌组55例和鳞癌组28例)和健康对照(对照组)50例,采集血清标本,提取并检测血清外泌体miR-205-5p/miR-152-5p联合相对表达量。比较NSCLC组和对照组的表达量,比较腺癌组、鳞癌组和对照组的表达量,使用多重线性回归分析表达量与性别、年龄、吸烟史、肿瘤大小、淋巴结转移的关联性,采用ROC曲线评价血清外泌体miR-205-5p/miR-152-5p联合相对表达量的诊断效能。结果对照组、NSCLC组、腺癌组、鳞癌组的miR-205-5p/miR-152-5p相对表达量分别为17.76±4.27、20.52±5.51、21.79±5.12、18.02±5.48;NSCLC组高于对照组(t=3.027,P=0.003),腺癌组、鳞癌组、对照组3组间比较差异有统计学意义(F=10.412,P<0.001),腺癌组高于鳞癌组(P=0.001)和对照组(P<0.001),鳞癌组与对照组间差异无统计学意义(P=0.823)。多元线性回归分析结果显示,淋巴结转移情况与相对表达量存在关联性(P=0.037)。对NSCLC的诊断效能评估,曲线下面积为0.671(95%CI:0.579~0.764),截断值为18.493,灵敏度为73.3%,特异度为64.0%。对肺腺癌的诊断效能评估,曲线下面积为0.738(95%CI:0.642~0.883),截断值为18.495,灵敏度为78.2%,特异度为64.0%。对肺鳞癌的诊断效能评估,曲线下面积为0.541(95%CI:0.399~0.684),无统计学意义。结论血清外泌体miR-205-5p/miR-152-5p联合相对表达量在早期NSCLC(主要为早期肺腺癌)患者中升高,对早期NSCLC诊断具有辅助价值。

关键词: miR-205-5p, miR-152-5p, 肺腺癌, 肺鳞癌, 非小细胞肺癌

Abstract: Objective To study the comprehensive expression and diagnosis value of serum exosomal miR-205-5p and miR-152-5p for early non-small cell lung cancer(NSCLC). Methods The objects were divided into the NSCLC group (n=83), which were further divided into the adenocarcinoma group (n=55) and squamous cell carcinoma group (n=28), and the control group (n=50). The TNM stage of NSCLC patients was 0-II. Serum samples were collected, the exosomal miRNA were extracted, then the comprehensive expressions of miR-205-5p and miR-152-5p were detected. The comprehensive expression between the NSCLC group and control group, and among adenocarcinoma group, squamous cell carcinoma group and control group were compared. Multiple linear regression was used to analyze the correlation between expression level and gender, age, smoking history, tumor size and lymph node metastasis. The diagnostic 山东大学学报 (医学版)57卷10期 -郑清月,等.血清外泌体miR-205-5p/miR-152-5p对早期非小细胞肺癌的诊断价值 \=-value of the comprehensive expression of miR-205-5p and miR-152-5p was evaluated with receiver operating characteristic(ROC)curve. Results The comprehensive expressions of control group, NSCLC group, adenocarcinoma group and squamous carcinoma group were 17.76±4.27, 20.52±5.51, 21.79±5.12, and 18.02±5.48, respectively. The expression was significantly higher in the NSCLC group than that in the control group (t=3.027,P=0.003). There were statistically significant differences among adenocarcinoma group, squamous cell carcinoma group and control group (F=10.412,P<0.001). The comprehensive expression of miR-205-5p/miR-152-5p was significantly higher in the adenocarcinoma group than that in the squamous cell carcinoma group (P=0.001) and the control group (P<0.001). The expression in the squamous cell carcinoma group and control group had no difference (P=0.823). Multiple linear regression analysis showed correlation between lymph node metastasis and expression level (P=0.037). For evaluation of diagnostic value of NSCLC, the area under the ROC curve(AUC)was 0.671(95%CI: 0.579-0.764),the cutoff value was 18.493, and the sensitivity and specificity were respective 73.3% and 64.0%. For evaluation of diagnostic value of lung adenocarcinoma, the AUC was 0.738(95%CI:0.642-0.883), the cutoff value was 18.495, the sensitivity and specificity were respective 78.2% and 64.0%. There was no diagnostic value for lung squamous cell carcinoma, with the AUC being 0.541(95%CI:0.399-0.684). Conclusion The comprehensive relative expressions of serum exosomal miR-205-5p and miR-152-5p are increased in early NSCLC patients, mainly in early lung adenocarcinoma patients. It has auxiliary value for early diagnosis of NSCLC.

Key words: miRNA-205-5p, miRNA-152-5p, Lung adenocarcinoma, Lung squamous cell carcinoma, Non-small cell lung cancer

中图分类号:

R734.2

郑清月,赵秋红,渠香云,董肇楠,马雪情,贾云莉. 血清外泌体miR-205-5p/miR-152-5p对早期非小细胞肺癌的诊断价值[J]. 山东大学学报 (医学版), 2019, 57(10): 101-106.

ZHENG Qingyue, ZHAO Qiuhong, QU Xiangyun, DONG Zhaonan, MA Xueqing, JIA Yunli. Diagnosis value of serum exosome miR-205-5p/miR-152-5p on early non-small cell lung cancer[J]. Journal of Shandong University (Health Sciences), 2019, 57(10): 101-106.

参考文献

[1] Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries [J]. CA Cancer J Clin, 2018, 68(6):394-424.
[2] Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016 [J]. CA Cancer J Clin, 2016, 66(1):7-30.
[3] 王传新. 外泌体生物标志物与肿瘤发生发展的研究进展[J].山东大学学报(医学版), 2018, 56(10): 18-23. WANG Chuanxin. Research progress of exosomes biomarkers in tumor development [J]. Journal of Shangdong University(Health Sciences), 2018, 56(10): 18-23.
[4] 李汉成,周玉婷,李婵,等. 外泌体源性微小RNA在疾病诊治中的研究现状[J].中国临床药理学杂志, 2017, 33(24): 2646-2652. LI Hancheng, ZHOU Yuting, LI Chan, et al. Research status of exosome-derived microRNA in diagnosis and treatment [J]. Chin J Clin Pharmacol, 2017, 33(24): 2646-2652.
[5] Maia J, Caja S, Strano Moraes MC, et al. Exosome-based cell-cell communication in the tumor microenvironment [J]. Front Cell Dev Biol, 2018, 6(2): 18.
[6] 罗详冲,刘晶晶,朱家宏,等.外泌体在肺癌中的研究进展[J].现代肿瘤医学, 2019, 27(9): 1651-1654. LUO Xiangchong, LIU Jingjing, ZHU Jiahong, et al. Research progress of exosomes in lung cance [J]. Modern Oncolog, 2019, 27(9): 1651-1654.
[7] Mathai RA, Vidya RVS, Reddy BS, et al. Potential utility of liquid biopsy as a diagnostic and prognostic tool for the assessment of solid tumors: implications in the precision oncology [J]. Clin Med, 2019, 8(3). pii: E373. doi: 10.3390/jcm8030373.
[8] Song ZP, Wang SS, Liu Y. The diagnostic accuracy of liquid exosomes for lung cancer detection: a meta-analysis [J]. OncoTargets and Therapy, 2019, 12(12): 181-192.
[9] Li CY, Yin YH, Liu X,et al. Non-small cell lung cancer associated microRNA expression signature: integrated bioinformatics analysis, validation and clinical significance [J]. Oncotarget, 2017, 8(15): 24564-24578.
[10] Li LM, Liu H, Liu XH, et al. Clinical significance of exosomal miRNAs and proteins in three human cancers with high mortality in China [J].Oncol Lett, 2019, 17(1): 11-22.
[11] Switlika W, Karbownikb MS, Suwalskic M, et al. miR-30a-5p together with miR-210-3p as a promising biomarker for non-small cell lung cancer: a preliminary study [J]. Cancer Biomark, 2018, 21(2): 479-488.
[12] Reclusa P, Taverna S, Pucci M, et al. Exosomes as diagnostic and predictive biomarkers in lung cancer [J]. J Thorac Dis, 2017, 9(13): 1373-1382.
[13] Zhu JJ, Zeng YY, Xu C, et al. Expression profile analysis of microRNAs and downregulated miR-486-5p and miR-30a-5p in non-small cell lung cancer [J]. Oncol Rep, 2015, 34(4): 1779-1786.
[14] 颜晓慧,安泰学,覃思华,等.血清外泌体miR-21在肺癌中的表达水平及诊断效能[J].实用医学杂志, 2017, 33(16): 2666-2669. YAN Xiaohui, AN taixue, TAN Sihua, et al. Expression level and diagnosis performance of serum exosomal miR-21 in lung cancer [J]. The Journal of Practical Medicine, 2017, 33(16): 2666-2669.
[15] 刘玉山,闫红江,李春雨.血清外泌体miRNA-184在非小细胞肺癌中的表达水平及其诊断效能[J].癌症进展, 2019, 17(4): 411-414. LIU Yushan, YAN Hongjiang, LI Chunyu. Expression of serum exosome miRNA-184 in non-small cell lung cancer and its diagnostic efficiency [J]. Oncology Progress, 2019, 17(4): 411-414.
[16] 魏萍,杜鲁涛,王卿,等.血清外泌体miR-20b-5p 对非小细胞肺癌的诊断价值[J].山东大学学报(医学版), 2019, 57(4): 91-96. WEI Ping, DU Lutao, WANG Qing, et al. Diagnostic value of serum exosomal miR-20b-5p for non-small cell lung cancer [J]. Journal of Shangdong University(Health Sciences), 2019, 57(4): 91-96.
[17] Markou AN, Lianidou ES. The impact of pre-analytical factors on the reliability of miRNA measurements [J]. Current Pathobiology Reports, 2019, 7(2): 29-33.
[18] Cai J, Fang L, Huang Y, et al. miR-205 targets PTEN and PHLPP2 to augment AKT signalling and drive malignant phenotypes in non-small cell lung cancer [J]. Cancer Res, 2013, 73(17): 5402-5415.
[19] Wang Y, Xu YM, Zou YQ, et al. Identification of differential expressed PE exosomal miRNA in lung adenocarcinoma, tuberculosis, and other benign lesions [J]. Medicine, 2017, 96(44): e8301. doi: 10.1097/MD.0000000000008361.
[20] Chen X, Hu Z, Wang W, et al. Identification of ten serum microRNAs from a genome-wide serum microRNA expression profile as novel noninvasive biomarkers for non-small cell lung cancer diagnosis [J]. Int J Cancer, 2012, 130(7): 1620-1628.
[21] Huang MX. Down-expression of circulating micro ribonucleic acid(miRNA)-148/152 family in plasma samples of non-small cell lung cancer patients [J]. J Cancer Res Ther, 2016, 12(2): 671-675.
[22] Yang JS, Li BJ, Lu HW, et al. Serum miR-152, miR-148a, miR-148b, and miR-21 as novel biomarkers in non-small cell lung cancer screening [J]. Tumour Biol, 2015, 36(4): 3035-3042.
[23] Su Y, Wang Y, Zhou H, et al. MicroRNA-152 targets ADAM17 to suppress NSCLC progression [J]. FEBS Lett, 2014, 588(10): 1983-1988.
[24] Zhang YJ, Liu XC, Du J, et al. MiR-152 regulates metastases of non-small cell lung cancer cells by targetingneuropilin-1 [J]. Int J Clin Exp Pathol, 2015, 8(11): 14235-14240.
[25] Yerukala Sathipati S, Ho SY. Identifying the miRNA signature associated with survival time in patients with lung adenocarcinoma using miRNA expression profiles [J]. Sci Rep, 2017, 7(1): 7507. doi: 10.1038/s41598-017-07739-y.

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