Circulating microRNA-422a is associated with lymphatic metastasis in lung cancer

Abstract

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.

Keywords: biomarker; lung cancer; lymphatic metastasis; miR-422a; microRNA.

Figure 1. Microarray analysis of miRNAs of the metastatic and non-metastatic lymph nodes from five patients with lung cancer

Figure 2. Expression of candidate miRNAs in training cohort of 26 lung cancer with or without lymphatic metastasis and five patients with benign lung disease

Figure 3. The accuracy of plasma circulating candidate miRNAs in the diagnosis of lymphatic metastasis in training cohort of 26 lung cancer patients

Figure 4. The accuracy of known tumor markers in the diagnosis of lymphatic metastasis in training cohort of lung cancer patients

Figure 5. Validation of miR-422a as a biomarker for lymph nodes metastasis

A. The accuracy of miR-422a in the diagnosis of lymphatic metastasis in validation cohort of 51 lung cancer patients. B. miR-422a expression data from both of training and validation cohorts were normalized and integrated. The diagnostic value of miR-422a in predicting lymphatic metastasis in all patients was analyzed.