Faculty Collaboration Database

MicroRNA-31 predicts the presence of lymph node metastases and survival in patients with lung adenocarcinoma. Clin Cancer Res 2013 Oct 01;19(19):5423-33

Date

08/16/2013

Pubmed ID

23946296

Pubmed Central ID

PMC3823052

DOI

10.1158/1078-0432.CCR-13-0320

Scopus ID

2-s2.0-84886420851 (requires institutional sign-in at Scopus site)   96 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.

Author List

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

Author

Victor X. Jin PhD Professor in the Institute for Health and Equity department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adenocarcinoma
Aged
Aged, 80 and over
Cell Line, Tumor
DNA Methylation
Female
Gene Expression
Gene Expression Profiling
Genetic Vectors
Humans
Lentivirus
Lung Neoplasms
Lymph Nodes
Lymphatic Metastasis
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