非小细胞肺癌患者外周血中lncRNA NEAT1的表达及诊断意义
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摘要
目的探究肺癌患者血浆中lncRNA NEAT1的表达水平以及对非小细胞肺癌的诊断价值。方法采用qRT-PCR技术检测258例非小细胞肺癌患者、115例肺部良性病变患者及70例健康对照外周血血浆样本中NEAT1的表达水平,比较其在血浆中的差异表达;分析NEAT1表达水平与肺癌患者临床特征的相关性;绘制ROC曲线分析血浆NEAT1水平对非小细胞肺癌的诊断价值。结果非小细胞肺癌患者血浆NEAT1水平较对照样本高表达(P<0.01);血浆NEAT1水平与非小细胞肺癌患者年龄、肿瘤大小相关,在>60岁组及肿瘤大小>3 cm组高表达,差异具有统计学意义(P<0.05);ROC曲线结果显示血浆NEAT1水平对区分非小细胞肺癌、早期非小细胞肺癌(Ⅰ期+Ⅱ期)、肿瘤大小≤3 cm的非小细胞肺癌与对照均有诊断价值,ROC曲线下面积分别为0.72、0.73、0.67。血浆NEAT1水平对于区分肿瘤大小≤3 cm的非小细胞肺癌与对照具有较高的灵敏度(93%)和阴性预测值(94%)。结论 NEAT1在非小细胞肺癌血浆中高表达,NEAT1具有作为非小细胞肺癌诊断标志物的潜能及肺癌早期辅助诊断价值。
Objective To investigate the expression level and diagnostic value of lncRNA NEAT1 in the plasma of patients with non-small cell lung cancer(NSCLC). Methods qRT-PCR was used to detect the expression level of NEAT1 in plasma samples of 258 patients with NSCLC, 115 patients with benign lung diseases and 70 healthy controls, and then the differential expression levels of NEAT1 were compared in the 3 groups. The correlation between the expression level of NEAT1 in plasma and the clinical characteristics of patients with NSCLC was analyzed. Receiver operating characteristic(ROC) curve analysis was used to analyze the diagnostic value of the NEAT1 level in plasma for NSCLC. Results In the NSCLC patients, the plasma level of NEAT1 was significantly higher than that in the healthy controls(P<0.01). The expression level of NEAT1 in the plasma was correlated with the age and tumor size of NSCLC patients, and was highly expressed in the >60 year-old group and the group whith tumor size >3 cm, with statistically significant differences(P<0.05). ROC curve results showed that plasma NEAT1 level had value for diagnosis of NSCLC, early stage NSCLC(stageⅠ+stageⅡ) or patients whose tumor size was equal to or less than 3 cm, with the areas under the curve of 0.72, 0.73 and 0.67, respectively. The plasma level of NEAT1 had a higher sensitivity(93%) as well as a higher negative predictive value(94%) to distinguish NSCLC with the tumor size ≤3 cm. Conclusion NEAT1 is highly expressed in the plasma of NSCLC patients. NEAT1 could be used as a potential diagnostic marker for NSCLC, and shows early diagnostic value for lung cancer.
Objective To investigate the expression level and diagnostic value of lncRNA NEAT1 in the plasma of patients with non-small cell lung cancer(NSCLC). Methods qRT-PCR was used to detect the expression level of NEAT1 in plasma samples of 258 patients with NSCLC, 115 patients with benign lung diseases and 70 healthy controls, and then the differential expression levels of NEAT1 were compared in the 3 groups. The correlation between the expression level of NEAT1 in plasma and the clinical characteristics of patients with NSCLC was analyzed. Receiver operating characteristic(ROC) curve analysis was used to analyze the diagnostic value of the NEAT1 level in plasma for NSCLC. Results In the NSCLC patients, the plasma level of NEAT1 was significantly higher than that in the healthy controls(P<0.01). The expression level of NEAT1 in the plasma was correlated with the age and tumor size of NSCLC patients, and was highly expressed in the >60 year-old group and the group whith tumor size >3 cm, with statistically significant differences(P<0.05). ROC curve results showed that plasma NEAT1 level had value for diagnosis of NSCLC, early stage NSCLC(stageⅠ+stageⅡ) or patients whose tumor size was equal to or less than 3 cm, with the areas under the curve of 0.72, 0.73 and 0.67, respectively. The plasma level of NEAT1 had a higher sensitivity(93%) as well as a higher negative predictive value(94%) to distinguish NSCLC with the tumor size ≤3 cm. Conclusion NEAT1 is highly expressed in the plasma of NSCLC patients. NEAT1 could be used as a potential diagnostic marker for NSCLC, and shows early diagnostic value for lung cancer.
引文
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[20] 罗泳林,陆爱英,蔡永林,等. 血浆长链非编码RNA NEAT1和H19及MALAT1在鼻咽癌中的表达及临床意义[J]. 中国耳鼻咽喉颅底外科杂志,2018,24(3):230-235. DOI:10.11798/j.issn.1007-1520.201803008. LUO Y L,LU A Y,CAI Y L, et al. Expression and clinical significance of plasma long noncoding RNA NEAT1, H19 and MALAT1 in nasopharyngeal carcinoma[J].Chin J Otorhinolaryngol-Skull Base Surg, 2018,24(3): 230-235. DOI:10.11798/j.issn.1007-1520.201803008.
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[22] HU X, BAO J, WANG Z, et al. The plasma lncRNA acting as fingerprint in non-small-cell lung cancer[J]. Tumour Biol, 2016, 37(3): 3497-3504. DOI: 10.1007/s13277-015-4023-9.
[2] CHEN W, ZHENG R, BAADE P D, et al. Cancer statistics in China, 2015[J]. CA Cancer J Clin, 2016, 66(2): 115-132. DOI: 10.3322/caac.21338.
[3] KHANDELWAL A, BACOLLA A, VASQUEZ K M, et al. Long non-coding RNA: A new paradigm for lung cancer[J]. Mol Carcinog, 2015, 54(11): 1235-1251. DOI: 10.1002/mc.22362.
[4] SU L, HAN D, WU J, et al. Skp2 regulates non-small cell lung cancer cell growth by Meg3 and miR-3163[J]. Tumour Biol, 2016, 37(3): 3925-3931. DOI: 10.1007/s13277-015-4151-2.
[5] MA S, DENG X, YANG Y, et al. The lncRNA LINC00675 regulates cell proliferation, migration, and invasion by affecting Wnt/β-catenin signaling in cervical cancer[J]. Biomed Pharmacother, 2018, 108: 1686-1693. DOI: 10.1016/j.biopha.2018.10.011.
[6] WANG J J, YANG Y C, SONG Y X, et al. Long non-coding RNA AB007962 is downregulated in gastric cancer and associated with poor prognosis[J]. Oncol Lett, 2018, 16(4): 4621-4627. DOI: 10.3892/ol.2018.9169.
[7] WANG F, XIE C, ZHAO W, et al. Long non-coding RNA CARLo-5 expression is associated with disease progression and predicts outcome in hepatocellular carcinoma patients[J]. Clin Exp Med, 2017, 17(1): 33-43. DOI: 10.1007/s10238-015-0395-9.
[8] CHEN Y, YU X, XU Y, et al. Identification of dysregulated lncRNAs profiling and metastasis-associated lncRNAs in colorectal cancer by genome-wide analysis[J]. Cancer Med, 2017, 6(10): 2321-2330. DOI: 10.1002/cam4.1168.
[9] LIU A, ZHANG Z, XU W, et al. Overexpression of long non-coding RNA n346372 in bladder cancer tissues is associated with a poor prognosis[J]. Mol Med Rep, 2018, 18(6): 5437-5444. DOI: 10.3892/mmr.2018.9597.
[10] YANG C, LI Z, LI Y, et al. Long non-coding RNA NEAT1 overexpression is associated with poor prognosis in cancer patients: a systematic review and meta-analysis[J]. Oncotarget, 2017, 8(2): 2672-2680. DOI: 10.18632/oncotarget.13737.
[11] QI L, LIU F, ZHANG F, et al. lncRNA NEAT1 competes against let-7a to contribute to non-small cell lung cancer proliferation and metastasis[J]. Biomed Pharmacother, 2018, 103: 1507-1515. DOI: 10.1016/j.biopha.2018.04.053.
[12] LI S, YANG J, XIA Y, et al. Long Noncoding RNA NEAT1 Promotes Proliferation and Invasion via Targeting miR-181a-5p in Non-Small Cell Lung Cancer[J]. Oncol Res, 2018, 26(2): 289-296. DOI: 10.3727/096504017 X15009404458675.
[13] QUAN J, PAN X, ZHAO L, et al. LncRNA as a diagnostic and prognostic biomarker in bladder cancer: a systematic review and meta-analysis[J]. Onco Targets Ther, 2018, 11: 6415-6424. DOI: 10.2147/OTT.S167853.
[14] ZOU Y, ZHONG Y, WU J, et al. Long non-coding PANDAR as a novel biomarker in human cancer: A systematic review[J]. Cell Prolif, 2018, 51(1): e12422. DOI:10.1111/cpr.12422.
[15] 董友玲,高红梅,陈文丽,等. 肺癌早期诊断方法的研究进展[J]. 中华灾害救援医学, 2017,5(1): 55-58. DOI:10.13919/j.issn.2095-6274.2017.01.010. DONG Y L, GAO H M, CHEN W L, et al. Early diagnosis of lung cancer:a brief review[J].Chin J Disaster Med,2017,5(1):55-58.DOI:10.13919/j.i-ssn.2095-6274.2017.01.010.
[16] SCHMITT A M, CHANG H Y. Long noncoding RNAs in cancer pathways[J]. Cancer Cell, 2016, 29(4): 452-463. DOI:10.1016/j.ccell.2016.03.010.
[17] MA X, WANG X, YANG C, et al. DANCR acts as a diagnostic biomarker and promotes tumor growth and metastasis in hepatocellular carcinoma[J]. Anticancer Res, 2016, 36(12): 6389-6398. DOI: 10.21873/anticanres.11236.
[18] WU Y, YANG L, ZHAO J, et al. Nuclear-enriched abundant transcript 1 as a diagnostic and prognostic biomarker in colorectal cancer[J]. Mol Cancer, 2015, 14: 191. DOI: 10.1186/s12943-015-0455-5.
[19] DING X, ZHANG Y, YANG H, et al. Long non-coding RNAs may serve as biomarkers in breast cancer combined with primary lung cancer[J]. Oncotarget, 2017, 8(35): 58210-58221. DOI: 10.18632/oncotarget.17356.
[20] 罗泳林,陆爱英,蔡永林,等. 血浆长链非编码RNA NEAT1和H19及MALAT1在鼻咽癌中的表达及临床意义[J]. 中国耳鼻咽喉颅底外科杂志,2018,24(3):230-235. DOI:10.11798/j.issn.1007-1520.201803008. LUO Y L,LU A Y,CAI Y L, et al. Expression and clinical significance of plasma long noncoding RNA NEAT1, H19 and MALAT1 in nasopharyngeal carcinoma[J].Chin J Otorhinolaryngol-Skull Base Surg, 2018,24(3): 230-235. DOI:10.11798/j.issn.1007-1520.201803008.
[21] JIANG N, MENG X, MI H, et al. Circulating lncRNA XLOC_009167 serves as a diagnostic biomarker to predict lung cancer[J]. Clin Chim Acta, 2018, 486: 26-33. DOI: 10.1016/j.cca.2018.07.026.
[22] HU X, BAO J, WANG Z, et al. The plasma lncRNA acting as fingerprint in non-small-cell lung cancer[J]. Tumour Biol, 2016, 37(3): 3497-3504. DOI: 10.1007/s13277-015-4023-9.