title: Identification of miR-374a as a prognostic marker for survival in patients with early-stage nonsmall cell lung cancer.
abstract: 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.
authors: Department of Biotechnology, Institute of Molecular and Cell Biology, University of Tartu, Riia 23, 51010 Tartu, Estonia.
authors: Urmo
authors: U
authors: Võsa
authors: Tõnu
authors: T
authors: Vooder
authors: Raivo
authors: R
authors: Kolde
authors: Krista
authors: K
authors: Fischer
authors: Kristjan
authors: K
authors: Välk
authors: Neeme
authors: N
authors: Tõnisson
authors: Retlav
authors: R
authors: Roosipuu
authors: Jaak
authors: J
authors: Vilo
authors: Andres
authors: A
authors: Metspalu
authors: Tarmo
authors: T
authors: Annilo
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D015536:Down-Regulation; D042241:Early Diagnosis; D004957:Estonia; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009367:Neoplasm Staging; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D018570:Risk Assessment; D016019:Survival Analysis; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs