Wu Lina, Hu Bo, Zhao Bingtian, Liu Yinan, Yang Yue, Zhang Lijian, Chen Jinfeng
Central Laboratory, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Beijing Cancer Hospital & Institute, Peking University Cancer Hospital, Beijing, China.
Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Department of Thoracic Surgery II, Peking University School of Oncology, Beijing Cancer Hospital & Institute, Beijing, China.
Oncotarget. 2017 Jun 27;8(26):42173-42188. doi: 10.18632/oncotarget.15025.
To identify specific circulating microRNAs that were associated with the lymphatic metastasis in lung cancer, we performed miRNA microarray analysis of lymph node with and without metastasis from five lung cancer patients. Top six differentially expressed miRNAs were selected for further validation. A training cohort of 26 patients with lung cancer was firstly recruited and the selected miRNAs in the plasma samples were investigated. miRNA-422a, with highest diagnostic accuracy in lymphatic metastasis was identified (AUC, area under the receiver operating characteristic curve, 0.744; 95%CI, 0.570-0.918). The diagnostic value of miR-422a was also demonstrated by a validation cohort of 51 lung cancer patients (AUC, 0.880; 95%CI, 0.787-0.972). Moreover, a high diagnostic value was also observed after integrated analysis of training and validation cohorts (AUC, 0.792; 95%CI, 0.688-0.896). The odds ratio of high miR-422a expression for lymphatic metastasis in lung cancer was 13.645 (95%CI, 2.677-69.553) after adjustment of the potential confounding factors. Furthermore, we predicted the target genes of miR-422a by combining the online database, miRcords, and the data from GEO and TCGA. Sixty-one target genes of miR-422a that might be involved in lymphatic metastasis in lung cancer were identified. And GO analysis suggested multiple target genes relatively concentrated in the biological processes of apoptosis, transport, and protein phosphorylation.
为了鉴定与肺癌淋巴转移相关的特定循环微小RNA，我们对5例肺癌患者有转移和无转移的淋巴结进行了miRNA微阵列分析。选择前六个差异表达的miRNA进行进一步验证。首先招募了一个由26例肺癌患者组成的训练队列，并对血浆样本中选定的miRNA进行了研究。鉴定出在淋巴转移中诊断准确性最高的miRNA-422a（受试者操作特征曲线下面积AUC为0.744；95%可信区间CI为0.570-0.918）。51例肺癌患者的验证队列也证实了miR-422a的诊断价值（AUC为0.880；95%CI为0.787-0.972）。此外，在对训练队列和验证队列进行综合分析后也观察到了较高的诊断价值（AUC为0.792；95%CI为0.688-0.896）。在调整潜在混杂因素后，肺癌中miR-422a高表达与淋巴转移的优势比为13.645（95%CI为2.677-69.553）。此外，我们通过结合在线数据库miRcords以及来自GEO和TCGA的数据预测了miR-422a的靶基因。鉴定出61个可能参与肺癌淋巴转移的miR-422a靶基因。基因本体（GO）分析表明多个靶基因相对集中在凋亡、转运和蛋白质磷酸化的生物学过程中。
