title: Identification of microRNAs differentially expressed between lung squamous cell carcinoma and lung adenocarcinoma.
abstract: Recent advances in the treatment of non-small cell lung cancer (NSCLC) with new agents require accurate histological subtyping at diagnosis to avoid the higher risk of an adverse response and to obtain the maximum therapeutic response. However, interobserver variability, tumor heterogeneity and the degree of differentiation may affect the decision concerning a pathological diagnosis of NSCLC. Therefore, the aim of this study was to identify specific microRNAs (miRNAs) as standardized biomarkers with high sensitivity and specificity in order to distinguish between squamous cell carcinoma (SCC) and adenocarcinoma (AC). Quantitative polymerase chain reaction (qPCR)‑based miRNA array analysis was performed to identify microRNAs differentially expressed between SCC and AC using 86 resected NSCLC samples in addition to adjacent normal tissues. The results were confirmed by independent qRT-PCR assays with the same test samples and 88 additional validation samples, and from this we evaluated the usefulness of the identified miRNAs as biomarkers to distinguish between SCC and AC. Three miRNAs (hsa-miR-196b, hsa-miR-205 and hsa-miR-375) were identified. Discriminant analysis combining the three miRNAs appeared to distinguish SCC from AC accurately in the test and validation samples, demonstrating a sensitivity and specificity of 76 and 80%, and 85 and 83%, respectively. hsa-miR-196b, hsa-miR-205 and hsa-miR-375 were identified as biomarkers capable of distinguishing between lung SCC and lung AC. These newly identified miRNAs may prove to be highly valuable molecular markers for the classification of NSCLC histological subtypes and may contribute to the pathogenesis of each subtype of NSCLC.
authors.affiliation: Department of Pulmonary Medicine, School of Medicine, Keio University, Tokyo 160-8582, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Hamamoto
authors.forename: Kenzo
authors.initials: K
authors.lastname: Soejima
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yoda
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Naoki
authors.forename: Sohei
authors.initials: S
authors.lastname: Nakayama
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Satomi
authors.forename: Hideki
authors.initials: H
authors.lastname: Terai
authors.forename: Shinnosuke
authors.initials: S
authors.lastname: Ikemura
authors.forename: Takashi
authors.initials: T
authors.lastname: Sato
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yasuda
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Michiie
authors.initials: M
authors.lastname: Sakamoto
authors.forename: Toru
authors.initials: T
authors.lastname: Takebayashi
authors.forename: Tomoko
authors.initials: T
authors.lastname: Betsuyaku
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009367:Neoplasm Staging; D012372:ROC Curve; D015203:Reproducibility of Results; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; C542543:MIRN196 microRNA, human; C534425:MIR205, human; C540933:MIRN375 microRNA, human