title: Pulmonary Carcinoids and Low-Grade Gastrointestinal Neuroendocrine Tumors Show Common MicroRNA Expression Profiles, Different from Adenocarcinomas and Small Cell Carcinomas.
abstract: It is still uncertain whether small cell lung carcinomas (SCLCs), pulmonary carcinoids, and the gastrointestinal neuroendocrine tumors (GI-NETs) have a common origin. MicroRNA (miRNA) expression may clarify their genetic relationships and origin.
  
  
  
  First, we compared the miRNA expression signature of formalin-fixed paraffin-embedded (FFPE) samples with frozen samples to verify the applicability of microarray analysis. Second, we compared the comprehensive miRNA expression patterns of pulmonary carcinoids and GI-NETs as well as other types of tumors and normal tissues from each organ using FFPE samples. These data were analyzed by hierarchical clustering and consensus clustering with nonnegative matrix factorization.
  
  
  
  We confirmed that FFPE samples retained the miRNA signatures. In the first hierarchical clustering comparing carcinoids/NETs with adenocarcinomas and normal tissues, most of the carcinoids (48/50) formed 1 major cluster with loose subpartitioning into each organ type, while all the adenocarcinomas (9/9) and normal tissues (15/15) formed another major cluster. The nonnegative matrix factorization approach largely matched the classification of the hierarchical clustering. In the additional cluster analysis comparing carcinoids/NETs with SCLCs, most carcinoids/NETs (17/22) formed a major cluster, while SCLCs (9/9) grouped together with pulmonary adenocarcinomas (3/3) and normal tissues (6/6) in another major cluster. Furthermore, a subset of miRNAs was successfully identified that exhibited significant expression in carcinoids/NETs.
  
  
  
  Carcinoids/NETs had a characteristic pattern of miRNA expression, suggesting a common origin for pulmonary carcinoids and GI-NETs. The expression profiles of pulmonary carcinoids and SCLCs were quite different, indicating the distinct histogenesis of these neuroendocrine neoplasms.
authors.affiliation: Division of Pathology, The Cancer Institute, Department of Pathology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research (JFCR), Koto-ku, Tokyo, Japan.
authors.forename: Toyoki
authors.initials: T
authors.lastname: Yoshimoto
authors.forename: Noriko
authors.initials: N
authors.lastname: Motoi
authors.forename: Noriko
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Hiroko
authors.initials: H
authors.lastname: Nagano
authors.forename: Masaru
authors.initials: M
authors.lastname: Ushijima
authors.forename: Masaaki
authors.initials: M
authors.lastname: Matsuura
authors.forename: Sakae
authors.initials: S
authors.lastname: Okumura
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Masashi
authors.initials: M
authors.lastname: Fukayama
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ishikawa
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D002276:Carcinoid Tumor / Q000378:metabolism* / Q000473:pathology; D018288:Carcinoma, Small Cell / Q000378:metabolism / Q000473:pathology; D016000:Cluster Analysis; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000378:metabolism* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D046228:Microarray Analysis; D008875:Middle Aged; D060787:Neoplasm Grading; D018358:Neuroendocrine Tumors / Q000378:metabolism* / Q000473:pathology; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs
keywords: Carcinoids (carcinoid tumors); Consensus clustering with nonnegative matrix factorization; Hierarchical clustering; MicroRNA; Microarray analysis