title: Gene expression profiles of small-cell lung cancers: molecular signatures of lung cancer.
abstract: To characterize the molecular mechanisms involved in the carcinogenesis and progression of small-cell lung cancer (SCLC) and identify molecules to be applied as novel diagnostic markers and/or for development of molecular-targeted drugs, we applied cDNA microarray profile analysis coupled with purification of cancer cells by laser-microbeam microdissection (LMM). Expression profiles of 32,256 genes in 15 SCLCs identified 252 genes that were commonly up-regulated and 851 transcripts that were down-regulated in SCLC cells compared with non-cancerous lung tissue cells. An unsupervised clustering algorithm applied to the expression data easily distinguished SCLC from the other major histological type of non-small cell lung cancer (NSCLC) and identified 475 genes that may represent distinct molecular features of each of the two histological types. In particular, SCLC was characterized by altered expression of genes related to neuroendocrine cell differentiation and/or growth such as ASCL1, NRCAM, and INSM1. We also identified 68 genes that were abundantly expressed both in advanced SCLCs and advanced adenocarcinomas (ADCs), both of which had been obtained from patients with extensive chemotherapy treatment. Some of them are known to be transcription factors and/or gene expression regulators such as TAF5L, TFCP2L4, PHF20, LMO4, TCF20, RFX2, and DKFZp547I048 as well as those encoding nucleotide-binding proteins such as C9orf76, EHD3, and GIMAP4. Our data provide valuable information for better understanding of lung carcinogenesis and chemoresistance.
authors.affiliation: Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Taniwaki
authors.forename: Yataro
authors.initials: Y
authors.lastname: Daigo
authors.forename: Nobuhisa
authors.initials: N
authors.lastname: Ishikawa
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takano
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Tsunoda
authors.forename: Wataru
authors.initials: W
authors.lastname: Yasui
authors.forename: Kouki
authors.initials: K
authors.lastname: Inai
authors.forename: Nobuoki
authors.initials: N
authors.lastname: Kohno
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics; D018288:Carcinoma, Small Cell / Q000235:genetics*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor