Hsu N Y, Ho H C, Chow K C, Lin T Y, Shih C S, Wang L S, Tsai C M
Department of Surgery, China Medical College Hospital, Taichung, Taiwan.
Cancer Res. 2001 Mar 15;61(6):2727-31.
By using mRNA differential display to examine specimens of non-small cell lung cancer (NSCLC), we have identified overexpression of dihydrodiol dehydrogenase (DDH) that was not detected in the corresponding normal lung tissue. Normally DDH is associated with catalysis of polycyclic aromatic hydrocarbons (PAHs) in the liver; in NSCLC cells, DDH expression would implicate an association with disease progression. In this study we investigated the prognostic significance of DDH expression in patients with NSCLC. By using immunohistochemistry, we measured DDH expression in 381 patients with NSCLC. The relationship between DDH expression and clinicopathological parameters (age, gender, smoking history, mitotic index, histological type, stage, cell differentiation, and lymphovascular invasion) was analyzed by chi2 analysis. Survival curves were plotted with the method of Kaplan-Meier, and statistical difference of survivals between different groups was compared by a log-rank test. Our results showed that DDH overexpression could be detected in 317 (83.2%) of 381 pathological sections and in 77.9% (60 of 77) of metastatic lymph nodes. Expression of DDH was confirmed by immunoblotting. Compared with patients with DDH overexpression in tumors, patients with low DDH expression had significantly lower incidence of early tumor recurrence and distant organ metastasis (46.7 versus 29.7%; P = 0.045). Interestingly, survival was also significantly better in patients with low DDH expression than in those with DDH overexpression (P = 0.0017). Using univariate analysis, we correlated three important factors, DDH overexpression, tumor stages, and gender, with poor prognosis for NSCLC patients. Nevertheless, biological function and involvement of DDH in the disease progression of NSCLC require additional studies.
通过使用mRNA差异显示技术检测非小细胞肺癌（NSCLC）标本，我们发现二氢二醇脱氢酶（DDH）在相应的正常肺组织中未被检测到，但在NSCLC中过表达。正常情况下，DDH与肝脏中多环芳烃（PAHs）的催化作用相关；在NSCLC细胞中，DDH的表达可能与疾病进展有关。在本研究中，我们调查了DDH表达在NSCLC患者中的预后意义。通过免疫组织化学方法，我们检测了381例NSCLC患者的DDH表达。采用卡方分析分析DDH表达与临床病理参数（年龄、性别、吸烟史、有丝分裂指数、组织学类型、分期、细胞分化和淋巴管侵犯）之间的关系。采用Kaplan-Meier方法绘制生存曲线，并通过对数秩检验比较不同组之间生存率的统计学差异。我们的结果显示，在381个病理切片中有317个（83.2%）可检测到DDH过表达，在77个转移淋巴结中有77.9%（60个）可检测到。通过免疫印迹法证实了DDH的表达。与肿瘤中DDH过表达的患者相比，DDH低表达的患者早期肿瘤复发和远处器官转移的发生率显著更低（46.7%对29.7%；P = 0.045）。有趣的是，DDH低表达患者的生存率也显著高于DDH过表达患者（P = 0.0017）。通过单因素分析，我们发现DDH过表达、肿瘤分期和性别这三个重要因素与NSCLC患者的不良预后相关。然而，DDH在NSCLC疾病进展中的生物学功能和作用还需要进一步研究。
