Identification of miR-374a as a prognostic marker for survival in patients with early-stage nonsmall cell lung cancer

Lung cancer is one of the deadliest types of cancer proven by the poor survival and high relapse rates after surgery. Recently discovered microRNAs (miRNAs), small noncoding RNA molecules, play a crucial role in modulating gene expression networks and are directly involved in the progression of a nu...

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Published in:Genes chromosomes & cancer 2011-10, Vol.50 (10), p.812-822
Main Authors: Võsa, Urmo, Vooder, Tõnu, Kolde, Raivo, Fischer, Krista, Välk, Kristjan, Tõnisson, Neeme, Roosipuu, Retlav, Vilo, Jaak, Metspalu, Andres, Annilo, Tarmo
Format: Article
Language:English
Subjects:
Adult
Aged
Biomarkers, Tumor - genetics
Carcinoma, Non-Small-Cell Lung - diagnosis
Carcinoma, Non-Small-Cell Lung - genetics
Carcinoma, Non-Small-Cell Lung - mortality
Carcinoma, Non-Small-Cell Lung - pathology
Cell migration
Cell survival
Differentiation
Down-Regulation
Early Diagnosis
Estonia
Female
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Humans
Lung - metabolism
Lung - pathology
Lung cancer
Lung Neoplasms - diagnosis
Lung Neoplasms - genetics
Lung Neoplasms - mortality
Lung Neoplasms - pathology
Male
MicroRNAs - genetics
Middle Aged
miRNA
Molecular Targeted Therapy
Neoplasm Staging
Prognosis
Real-Time Polymerase Chain Reaction
Risk Assessment
RNA
Signal transduction
Surgery
Survival Analysis
Tumorigenesis
Up-Regulation
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Summary:Lung cancer is one of the deadliest types of cancer proven by the poor survival and high relapse rates after surgery. Recently discovered microRNAs (miRNAs), small noncoding RNA molecules, play a crucial role in modulating gene expression networks and are directly involved in the progression of a number of human cancers. In this study, we analyzed the expression profile of 858 miRNAs in 38 Estonian nonsmall cell lung cancer (NSCLC) samples (Stage I and II) and 27 adjacent nontumorous tissue samples using Illumina miRNA arrays. We found that 39 miRNAs were up‐regulated and 33 down‐regulated significantly in tumors compared with normal lung tissue. We observed aberrant expression of several well‐characterized tumorigenesis‐related miRNAs, as well as a number of miRNAs whose function is currently unknown. We show that low expression of miR‐374a in early‐stage NSCLC is associated with poor patient survival. The combinatorial effect of the up‐ and down‐regulated miRNAs is predicted to most significantly affect pathways associated with cell migration, differentiation and growth, and several signaling pathways that contribute to tumorigenesis. In conclusion, our results demonstrate that expression of miR‐374a at early stages of NSCLC progression can serve as a prognostic marker for patient risk stratification and may be a promising therapeutic target for the treatment of lung cancer. © 2011 Wiley‐Liss, Inc.
ISSN:1045-2257
1098-2264
1098-2264
DOI:10.1002/gcc.20902