Discriminating between Terminal- and Non-Terminal Respiratory Unit-Type Lung Adenocarcinoma Based on MicroRNA Profiles

• Published in: PloS one Vol. 11; no. 8; p. e0160996
• Main Authors: Kim, Mi-Hyun, Cho, Jeong Su, Kim, Yeongdae, Lee, Chang Hun, Lee, Min Ki, Shin, Dong Hoon
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 30.08.2016; Public Library of Science (PLoS)
• Subjects: Adenocarcinoma; Adenocarcinoma - classification; Adenocarcinoma - genetics; Adenocarcinoma of Lung; Aged; Analysis; Biology and life sciences; Biomarkers, Tumor - genetics; Cancer therapies; Cytoplasm; Development and progression; Epidermal growth factor; Female; Gene expression; Gene Expression Profiling - methods; Gene Expression Regulation, Neoplastic; Genetic aspects; Hospitals; Humans; Internal medicine; Lung cancer; Lung Neoplasms - classification; Lung Neoplasms - genetics; Lungs; Male; Medical prognosis; Medical research; Medicine; Medicine and Health Sciences; MicroRNA; MicroRNAs; MicroRNAs - genetics; Middle Aged; miRNA; Mutation; Non-small cell lung cancer; Oligonucleotide Array Sequence Analysis - methods; Physiological aspects; Research and Analysis Methods; Ribonucleic acid; RNA; RNA, Viral - genetics; Rodents; Studies; Thoracic surgery; Tumorigenesis; South Korea; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0160996

Lung adenocarcinomas can be classified into terminal respiratory unit (TRU) and non-TRU types. We previously reported that non-TRU-type adenocarcinoma has unique clinical and morphological features as compared to the TRU type. Here we investigated whether micro (mi)RNA expression profiles can be used to distinguish between these two subtypes of lung adenocarcinoma. The expression of 1205 human and 144 human viral miRNAs was analyzed in TRU- and non-TRU-type lung adenocarcinoma samples (n = 4 each) by microarray. Results were validated by quantitative real-time (qRT-)PCR and in situ hybridization. A comparison of miRNA profiles revealed 29 miRNAs that were differentially expressed between TRU- and non-TRU adenocarcinoma types. Specifically, hsa-miR-494 and ebv-miR-BART19 were up regulated by > 5-fold, whereas hsa-miR-551b was down regulated by > 5-fold in the non-TRU relative to the TRU type. The miRNA signature was confirmed by qRT-PCR analysis using an independent set of paired adenocarcinoma (non-TRU-type, n = 21 and TRU-type, n = 12) and normal tissue samples. Non-TRU samples showed increased expression of miR-494 (p = 0.033) and ebv-miR-BART19 (p = 0.001) as compared to TRU-type samples. Both miRNAs were weakly expressed in the TRU type but strongly expressed in the non-TRU type. Neither subtype showed miR-551b expression. TRU- and non-TRU-type adenocarcinomas have distinct miRNA expression profiles, suggesting that tumorigenesis in lung adenocarcinoma occur via different pathways.