Carbonyl Reductase Expression and Its Clinical Significance in Non–Small-Cell Lung Cancer
Carbonyl Reductase Expression and Its Clinical Significance in Non–Small-Cell Lung Cancer
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DOI：
10.1158/1055-9965.epi-05-0060
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发表时间：
2005-08
影响因子：
3.8
通讯作者：
K. Takenaka;E. Ogawa;H. Oyanagi;H. Wada;F. Tanaka
中科院分区：
文献类型：
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作者：
K. Takenaka;E. Ogawa;H. Oyanagi;H. Wada;F. Tanaka
羰基还原酶（CBR）是一种细胞内nadph依赖的氧化还原酶，代谢前列腺素、类固醇、奎宁和蒽环类抗生素。许多实验研究表明，CBR在调节肿瘤进展中发挥重要作用，但CBR状态的临床意义尚不清楚。因此，我们对CBR mRNA在肺癌中的表达进行了回顾性研究。对59例非小细胞肺癌患者的肿瘤组织进行实时定量逆转录- pcr分析，探讨CBR表达的临床意义。采用抗cd34单克隆抗体（CD34-IMVD）和抗cd105单克隆抗体（CD105-IMVD）免疫组化法测定肿瘤内微血管密度。随着原发肿瘤的进展，CBR mRNA的表达显著降低（平均CBR mRNA/GAPDH mRNA， pT1为3.288 × 10−2，pT2为1.628 × 10−2，pT3-4为1.175 × 10−2,P = 0.02）。此外，CBR mRNA在有淋巴结累及的肿瘤中的表达似乎比无淋巴结累及的肿瘤有所降低（CBR mRNA/GAPDH mRNA的平均值分别为1.446 × 10−2和2.531 × 10−2），但差异无统计学意义（P = 0.09）。cbr高组的平均CD105-IMVD为59.2，显著低于cbr低组（130.6,P = 0.02），而cbr高组和cbr低组的平均cd34 - imvd无显著差异。cbr高患者5年生存率为68.3%，显著高于cbr低患者（36.5%,P = 0.03）。多因素分析证实cbr高表达是预测预后良好的重要因素（P = 0.04；相对危险度为0.39；95%可信区间为0.16-0.98）。在非小细胞肺癌中，CBR mRNA的表达是一个重要的预后因素，与肿瘤进展和血管生成呈负相关。
Carbonyl reductase (CBR) is a cytosolic NADPH-dependent oxidoreductase metabolizing prostaglandins, steroids, quinines, and anthracycline antibiotics. Many experimental studies have shown that CBR plays important roles in the 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. Tumor tissues obtained from 59 non–small-cell lung cancer patients were analyzed by quantitative real-time reverse transcription-PCR assay to reveal clinical significance of CBR expression. Angiogenesis was measured immunohistochemically as intratumoral microvessel density (IMVD) using anti-CD34 monoclonal antibody CD34-IMVD) and anti-CD105 monoclonal antibody (CD105-IMVD). CBR mRNA expression was significantly reduced along with progression of primary tumors (the mean CBR mRNA/GAPDH mRNA, 3.288 × 10−2 for pT1, 1.628 × 10−2 for pT2, and 1.175 × 10−2 for pT3-4 disease, respectively; P = 0.02). 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 × 10−2 and 2.531 × 10−2, respectively), whereas the difference did not reach a statistical significance (P = 0.09). The mean CD105-IMVD for CBR-high tumor was 59.2, which was significantly lower than that for CBR-low tumor (130.6, P = 0.02), whereas no significant difference between the mean CD34-IMVDs 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 = 0.03). A multivariate analysis confirmed that CBR-high expression was a significant factor to predict a favorable prognosis (P = 0.04; relative risk, 0.39; 95% confidence interval, 0.16-0.98). Expression of CBR mRNA was a significant prognostic factor in non–small-cell lung cancer and was inversely associated with tumor progression and angiogenesis.