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

Meng W, Ye Z, Cui R, Perry J, Dedousi-Huebner V, Huebner A, Wang Y, Li B, Volinia S, Nakanishi H, Kim T, Suh SS, Ayers LW, Ross P, Croce CM, Chakravarti A, Jin VX, Lautenschlaeger T
Clin Cancer Res. 2013 19 (19): 5423-33

PMID: 23946296 · PMCID: PMC3823052 · DOI:10.1158/1078-0432.CCR-13-0320

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.

©2013 AACR.

MeSH Terms (26)

Adenocarcinoma Adenocarcinoma of Lung Aged Aged, 80 and over Cell Line, Tumor DNA Methylation Female Gene Expression Gene Expression Profiling Genetic Vectors Humans Lentivirus Lung Neoplasms Lymphatic Metastasis Lymph Nodes Male MicroRNAs Middle Aged Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Neoplasm Staging Prognosis Promoter Regions, Genetic Reproducibility of Results Risk Factors Signal Transduction

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