MicroRNA-31 predicts the presence of lymph node metastases and survival in patients with lung adenocarcinoma

Wei Meng, Zhenqing Ye, Ri Cui, James Perry, Vaia Dedousi-Huebner, Alexander Huebner, Yao Wang, Bin Li, Stefano Volinia, Hiroshi Nakanishi, Taewan Kim, Sung Suk Suh, Leona W. Ayers, Patrick Ross, Carlo M. Croce, Arnab Chakravarti, Victor X. Jin, Tim Lautenschlaeger

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77 Scopus citations

Abstract

Purpose: 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. Experimental Design: 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 in vitro. Results: 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 (P=0.009, t test), and to be expressed at higher levels in adenocarcinoma tissue than in matched normal adjacent lung tissues (P < 0.0001, paired t 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 (P = 0.031, t test). In vitro 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 in silico analysis showed that low expression of miR-31 is associated with excellent survival for T2N0 patients. Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)5423-5433
Number of pages11
JournalClinical Cancer Research
Volume19
Issue number19
DOIs
StatePublished - Oct 1 2013

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Meng, W., Ye, Z., Cui, R., Perry, J., Dedousi-Huebner, V., Huebner, A., Wang, Y., Li, B., Volinia, S., Nakanishi, H., Kim, T., Suh, S. S., Ayers, L. W., Ross, P., Croce, C. M., Chakravarti, A., Jin, V. X., & Lautenschlaeger, T. (2013). MicroRNA-31 predicts the presence of lymph node metastases and survival in patients with lung adenocarcinoma. Clinical Cancer Research, 19(19), 5423-5433. https://doi.org/10.1158/1078-0432.CCR-13-0320