Cytochrome P450 expression (CYP) in non-small cell lung cancer.
The cytochrome P450 (CYP) is associated with tumor development and progression as well as activation of anti-cancer prodrugs and their metabolic clearance. In this study, we investigated the expression of aryl-hydrocarbon receptor (AH-R) and four CYPs (CYP1A1, CYP2A6, CYP2E1 and CYP3A) as putative diagnostic markers in 78 non-small cell lung cancers (NSCLC) along with clinical features of the patients. In non-small cell lung cancer, the expression of the five markers was mainly observed in adenocarcinoma but not in the most squamous cell cancers. The expression of them in adenocarcinoma was more frequent in females than in males, suggesting that a higher risk of women for developing lung adenocarcinoma might be associated with the frequent expression of AH-R and the CYPs. These factors were also more frequently expressed in early stage adenocarcinoma and more differentiated adenocarcinoma. Multiple types of CYPs are more frequently expressed in early stage of adenocarcinoma than in advanced stage of adenocarcinoma. There were positive relationships among AH-R, CYP1A1, CYP2E1 and CYP3A expressions in adenocarcinoma, which suggests a metabolite-mediated cross talk in the gene regulation of these markers. However, any of them was unrelated with the expression of CYP2A6, suggesting that the gene regulation of CYP2A6 in adenocarcinoma may be different from the other three CYPs. The expression frequency of CYP1A1 and CYP2E1 in tumors is independent of their genetic polymorphism. The survival of the patients with advanced adenocarcinoma expressing more than one of CYPs was lower rate than the patients with those expressing no CYPs, suggesting that the expression of the CYPs in advanced adenocarcinoma may be associated with poor survival. Our results suggest that AH-R and 4 CYPs may be good markers for the determination of quality of lung cancer. The information could be useful for the better management of lung cancer by molecular targeting therapy and selection of anti-cancer drug based on individual spectrum of the marker proteins. Therefore, the spectrum of CYP proteins in lung cancer could be useful for changing the present "order-made" therapy to the "tailor-made" therapy.
Oyama
Tsunehiro
T
Second Department of Surgery, University of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan. oyama@med.uoehu.ac.jp
Sugio
Kenji
K
Uramoto
Hidetaka
H
Kawamoto
Toshihiro
T
Kagawa
Norio
N
Nadaf
Sorena
S
Carbone
David
D
Yasumoto
Kosei
K
D000230:Adenocarcinoma / Q000175:diagnosis; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011110:Polymorphism, Genetic; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism
D014408:Biomarkers, Tumor; D018336:Receptors, Aryl Hydrocarbon; D003577:Cytochrome P-450 Enzyme System; D019392:Cytochrome P-450 CYP2E1; D019363:Cytochrome P-450 CYP1A1