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Background: Carbonyl reductase (CBR) is a cytosolic NADPH-dependent oxidoreductase metabolizing prostaglandins, steroids, quinines, and anthracycline antibiotics. Many experimental studies have demonstrated that CBR plays important roles in regulation of tumor progression, but clinical significance of CBR status remains unclear. Thus, we conducted a retrospective study on CBR mRNA expression in lung cancer. Methods: RNA was extracted from 11 lung cancer cell lines and 2 normal lung cell lines, and the expression of CBR mRNA was quantitatively evaluated by real-time RT-PCR assay. Angiogenesis was measured immunohistochemically as intratumoral microvessel density (IMVD) using anti-CD34 monoclonal antibody (mAb) (CD34-IMVD) and anti CD-105 mAb (CD105-IMVD). To reveal clinical significance of CBR expression, paired normal lung tissues and tumor tissues obtained from 94 NSCLC patients were also analyzed. Results: CBR mRNA expression was reduced in 9 of 11 lung cancer cell lines than in two normal human lung cell lines, but no significant difference was revealed. In analyses of resected tissues, there was no significant difference in the CBR mRNA expression between tumor tissues and normal lung tissues. CBR mRNA expression was significantly reduced along with progression of primary tumors (the mean CBR mRNA /GAPDHmRNA, 3.288 x 10-2 for pT1, 1.628 x 10-2 for pT2, and 1.175 x 10-2 for pT3-4 disease, respectively; p=0.019). Moreover, CBR mRNA expression in tumor with nodal involvement seemed to be reduced as compared with that in tumor without nodal involvement (the mean CBR mRNA/GAPDH mRNA, 1.446 x 10-2 and 2.531 x 10-2, respectively), whereas the difference did not reach a statistical significance (p=0.090). The mean CD105-IMVD for CBR-high tumor was 72.7, which was significantly lower than that for CBR-high tumor (137.0, p=0.019), whereas no significant difference between the mean CD34-IMVD for CBR-high tumor and CBR-low tumor was found. The 5-year survival rate of CBR-high patients was 68.3%, significantly higher than that of CBR-low patients (36.5%; p=0.026). A multivariate analysis confirmed that CBR-high expression was a significant factor to predict a favorable prognosis (p=0.044; relative risk, 2.562 with the 95% confidence interval 1.024-6.408). Conclusion: Expression of CBR mRNA was a significant prognostic factor in NSCLC in correlation with tumor progression and angiogenesis.

[Proc Amer Assoc Cancer Res, Volume 46, 2005]