title: Overexpression of the aldo-keto reductase family protein AKR1B10 is highly correlated with smokers' non-small cell lung carcinomas.
abstract: OBJECTIVE
  Squamous cell carcinoma (SCC) and adenocarcinoma of the lung are currently subject to similar treatment regimens despite distinct differences in histology and epidemiology. The aim of this study is to identify a molecular target with diagnostic and therapeutic values for SCC.
  
  
  METHODS
  Genes specifically up-regulated in SCC were explored through microarray analysis of 5 SCCs, 5 adenocarcinomas, 10 small cell lung carcinomas, 27 normal tissues, and 40 cancer cell lines. Clinical usefulness of these genes was subsequently examined mainly by immunohistochemical analysis.
  
  
  RESULTS
  Seven genes, including aldo-keto reductase family 1, member B10 (AKR1B10), were identified as SCC-specific genes. AKR1B10 was further examined by immunohistochemical analysis of 101 non-small cell lung carcinomas (NSCLC) and its overexpression was observed in 27 of 32 (84.4%) SCCs and 19 of 65 (29.2%) adenocarcinomas. Multiple regression analysis showed that smoking was an independent variable responsible for AKR1B10 overexpression in NSCLCs (P < 0.01) and adenocarcinomas (P < 0.01). AKR1B10 staining was occasionally observed even in squamous metaplasia, a precancerous lesion of SCC.
  
  
  CONCLUSIONS
  AKR1B10 was overexpressed in most cases with SCC, which is closely associated with smoking, and many adenocarcinoma cases of smokers. These results suggest that AKR1B10 is a potential diagnostic marker specific to smokers' NSCLCs and might be involved in tobacco-related carcinogenesis.
authors.affiliation: Genome Science Division and Laboratory for Systems Biology and Medicine, Research Center for Advanced Science and Technology, Graduate School of Medicine, University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8904, Japan.
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Fukumoto
authors.forename: Naoko
authors.initials: N
authors.lastname: Yamauchi
authors.forename: Hisashi
authors.initials: H
authors.lastname: Moriguchi
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Hippo
authors.forename: Akira
authors.initials: A
authors.lastname: Watanabe
authors.forename: Junji
authors.initials: J
authors.lastname: Shibahara
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Taniguchi
authors.forename: Shumpei
authors.initials: S
authors.lastname: Ishikawa
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Ito
authors.forename: Shogo
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Hiroko
authors.initials: H
authors.lastname: Iwanari
authors.forename: Mitsugu
authors.initials: M
authors.lastname: Hironaka
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ishikawa
authors.forename: Toshiro
authors.initials: T
authors.lastname: Niki
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Sohara
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Kodama
authors.forename: Masaharu
authors.initials: M
authors.lastname: Nishimura
authors.forename: Masashi
authors.initials: M
authors.lastname: Fukayama
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Dosaka-Akita
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Aburatani
mesh_terms: D000449:Aldehyde Reductase / Q000096:biosynthesis* / Q000235:genetics*; D000074408:Aldo-Keto Reductases; D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000209:etiology* / Q000235:genetics*; D016022:Case-Control Studies; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000209:etiology* / Q000235:genetics* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D012907:Smoking / Q000009:adverse effects*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
chemical_list: D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; C120471:AKR1B10 protein, human; D000074408:Aldo-Keto Reductases; D000449:Aldehyde Reductase