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


METHODS
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.
Authors' Affiliations: Department of Molecular Medicine, The University of Texas Health Science Center, San Antonio, Texas; Department of Radiation Oncology, Department of Molecular Virology, Immunology and Medical Genetics; Comprehensive Cancer Center; Department of Pathology, College of Medicine; Department of Surgery, Division of Thoracic Surgery, The Ohio State University, Columbus, Ohio; and Yanbian University College of Medicine, Ji Lin, China.
Wei
W
Meng
Zhenqing
Z
Ye
Ri
R
Cui
James
J
Perry
Vaia
V
Dedousi-Huebner
Alexander
A
Huebner
Yao
Y
Wang
Bin
B
Li
Stefano
S
Volinia
Hiroshi
H
Nakanishi
Taewan
T
Kim
Sung-Suk
SS
Suh
Leona W
LW
Ayers
Patrick
P
Ross
Carlo M
CM
Croce
Arnab
A
Chakravarti
Victor X
VX
Jin
Tim
T
Lautenschlaeger
D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D019175:DNA Methylation; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009367:Neoplasm Staging; D011379:Prognosis; D011401:Promoter Regions, Genetic; D015203:Reproducibility of Results; D012307:Risk Factors; D015398:Signal Transduction
C534612:MIRN31 microRNA, human; D035683:MicroRNAs; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3