Data from MicroRNA-31 Predicts the Presence of Lymph Node Metastases and Survival in Patients with Lung Adenocarcinoma

Abstract

<div>Abstract<p><b>Purpose:</b> We conducted genome-wide miRNA-sequencing (miRNA-seq) in primary cancer tissue from patients of lung adenocarcinoma to identify markers for the presence of lymph node metastasis.</p><p><b>Experimental Design:</b> Markers for lymph node metastasis identified by sequencing were validated in a separate cohort using quantitative PCR. After additional validation in the The Cancer Genome Atlas (TCGA) dataset, functional characterization studies were conducted <i>in vitro</i>.</p><p><b>Results:</b> MiR-31 was upregulated in lung adenocarcinoma tissues from patients with lymph node metastases compared with those without lymph node metastases. We confirmed miR-31 to be upregulated in lymph node-positive patients in a separate patient cohort (<i>P</i> = 0.009, <i>t</i> test), and to be expressed at higher levels in adenocarcinoma tissue than in matched normal adjacent lung tissues (<i>P</i> < 0.0001, paired <i>t</i> test). MiR-31 was then validated as a marker for lymph node metastasis in an external validation cohort of 233 lung adenocarcinoma cases of the TCGA (<i>P</i> = 0.031, <i>t</i> test). <i>In vitro</i> functional assays showed that miR-31 increases cell migration, invasion, and proliferation in an ERK1/2 signaling-dependent manner. Notably, miR-31 was a significant predictor of survival in a multivariate cox regression model even when controlling for cancer staging. Exploratory <i>in silico</i> analysis showed that low expression of miR-31 is associated with excellent survival for T<sub>2</sub>N<sub>0</sub> patients.</p><p><b>Conclusions:</b> We applied miRNA-seq to study microRNomes in lung adenocarcinoma tissue samples for the first time and potentially identified a miRNA predicting the presence of lymph node metastasis and survival outcomes in patients of lung adenocarcinoma. <i>Clin Cancer Res; 19(19); 5423–33. ©2013 AACR</i>.</p></div>