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Clinical Cancer Research Vol. 11, 1776-1785, March 2005
© 2005 American Association for Cancer Research


Imaging, Diagnosis, Prognosis

Overexpression of the Aldo-Keto Reductase Family Protein AKR1B10 Is Highly Correlated with Smokers' Non–Small Cell Lung Carcinomas

Shin-ichi Fukumoto1,8, Naoko Yamauchi3, Hisashi Moriguchi2, Yoshitaka Hippo1, Akira Watanabe1, Junji Shibahara3, Hirokazu Taniguchi3, Shumpei Ishikawa1, Hirotaka Ito1, Shogo Yamamoto1, Hiroko Iwanari5, Mitsugu Hironaka6, Yuichi Ishikawa4, Toshiro Niki3, Yasunori Sohara7, Tatsuhiko Kodama2, Masaharu Nishimura8, Masashi Fukayama3, Hirotoshi Dosaka-Akita9 and Hiroyuki Aburatani1

1 Genome Science Division and 2 Laboratory for Systems Biology and Medicine, Research Center for Advanced Science and Technology, and 3 Department of Pathology, Graduate School of Medicine, University of Tokyo; 4 Department of Pathology, Cancer Institute, Japanese Foundation for Cancer Research; and 5 Perseus Proteomics, Inc., Tokyo, Japan; Departments of 6 Pathology and 7 Thoracic Surgery, Jichi Medical School, Tochigi, Japan; and 8 First Department of Medicine and 9 Department of Medical Oncology, Hokkaido University Graduate School of Medicine, Sapporo, Japan

Requests for reprints: Hiroyuki Aburatani, Genome Science Division, Research Center for Advanced Science and Technology, University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8904, Japan. Phone: 81-3-5452-5235; Fax: 81-3-5452-5355; E-mail: haburata-tky{at}umin.ac.jp.

Purpose: 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.

Experimental Design: 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.

Conclusion: 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.

Key Words: microarray • squamous cell lung carcinoma • tobacco • retinoic acid • metaplasia




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Copyright © 2005 by the American Association for Cancer Research.