Zhou Xin, Wen Wei, Shan Xia, Zhu Wei, Xu Jing, Guo Renhua, Cheng Wenfang, Wang Fang, Qi Lian-Wen, Chen Yan, Huang Zebo, Wang Tongshan, Zhu Danxia, Liu Ping, Shu Yongqian
Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, PR China.
Department of Thoracic Surgery, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, PR China.
Oncotarget. 2017 Jan 24;8(4):6513-6525. doi: 10.18632/oncotarget.14311.
Differently expressed microRNAs (miRNAs) in the plasma of lung adenocarcinoma (LA) patients might serve as biomarkers for LA detection. MiRNA expression profiling was performed using Exiqon panels followed by the verification (30 LA VS. 10 healthy controls (HCs)) with quantitative reverse transcription polymerase chain reaction (qRT-PCR) in the screening phase. Identified miRNAs were confirmed through training (42 LA VS. 32 HCs) and testing stages (66 LA VS. 62 HCs) by using qRT-PCR based absolute quantification methods. A total of six up-regulated plasma miRNAs (miR-19b-3p, miR-21-5p, miR-221-3p, miR-409-3p, miR-425-5p and miR-584-5p) were identified. The six-miRNA panel could discriminate LA patients from HCs with areas under the receiver operating characteristic curve of 0.72, 0.74 and 0.84 for the training, testing and the external validation stage (33 LA VS. 30 HCs), respectively. All the miRNAs identified except miR-584-5p were significantly up-regulated in LA tissues. MiR-19-3p, miR-21-5p, miR-409-3p and miR-425-5p showed high expression in arterial plasma with borderline significance. Additionally, miR-19-3p, miR-21-5p and miR-221-3p were significantly up-regulated in exosomes extracted from LA peripheral plasma samples. In conclusion, we identified a six-miRNA panel in peripheral plasma which might give assistance to the detection of LA at least for Asian population to a certain extent.
肺腺癌(LA)患者血浆中差异表达的微小RNA(miRNA)可能作为LA检测的生物标志物。在筛选阶段,使用Exiqon芯片进行miRNA表达谱分析,随后通过定量逆转录聚合酶链反应(qRT-PCR)进行验证(30例LA患者与10例健康对照(HC))。通过基于qRT-PCR的绝对定量方法,在训练阶段(42例LA患者与32例HC)和测试阶段(66例LA患者与62例HC)对鉴定出的miRNA进行确认。共鉴定出6种上调的血浆miRNA(miR-19b-3p、miR-21-5p、miR-221-3p、miR-409-3p、miR-425-5p和miR-584-5p)。对于训练、测试和外部验证阶段(33例LA患者与30例HC),六miRNA组合分别以0.72、0.74和0.84的受试者工作特征曲线下面积区分LA患者与HC。除miR-584-5p外,所有鉴定出的miRNA在LA组织中均显著上调。miR-19-3p、miR-21-5p、miR-409-3p和miR-425-5p在动脉血浆中高表达,具有临界显著性。此外,miR-19-3p、miR-21-5p和miR-221-3p在从LA外周血样本中提取的外泌体中显著上调。总之,我们在外周血中鉴定出一个六miRNA组合,这可能至少在一定程度上有助于亚洲人群LA的检测。