Overexpression of the aldo-keto reductase family protein AKR1B10 is highly correlated with smokers' non-small cell lung carcinomas.
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.
Fukumoto
Shin-ichi
S
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.
Yamauchi
Naoko
N
Moriguchi
Hisashi
H
Hippo
Yoshitaka
Y
Watanabe
Akira
A
Shibahara
Junji
J
Taniguchi
Hirokazu
H
Ishikawa
Shumpei
S
Ito
Hirotaka
H
Yamamoto
Shogo
S
Iwanari
Hiroko
H
Hironaka
Mitsugu
M
Ishikawa
Yuichi
Y
Niki
Toshiro
T
Sohara
Yasunori
Y
Kodama
Tatsuhiko
T
Nishimura
Masaharu
M
Fukayama
Masashi
M
Dosaka-Akita
Hirotoshi
H
Aburatani
Hiroyuki
H
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
D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; C120471:AKR1B10 protein, human; D000074408:Aldo-Keto Reductases; D000449:Aldehyde Reductase