Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Athens, Athens, Greece.
Transl Oncol. 2012 Aug;5(4):288-96. doi: 10.1593/tlo.12223. Epub 2012 Aug 1.
l-DOPA decarboxylase (DDC) plays an essential role in the enzymatic synthesis of dopamine and alterations in its gene expression have been reported in several malignancies. Our objective was to analyze DDC messenger RNA (mRNA) and protein expression in laryngeal tissues and to evaluate the clinical implication of this molecule in laryngeal cancer. In this study, total RNA was isolated from 157 tissue samples surgically removed from 100 laryngeal cancer patients. A highly sensitive real-time polymerase chain reaction methodology based on SYBR Green I fluorescent dye was developed for the quantification of DDC mRNA levels. In addition, Western blot analysis was performed for the detection of DDC protein. DDC mRNA expression was revealed to be significantly downregulated in primary laryngeal cancer samples compared with their nonmalignant counterparts (P = .001). A significant negative association was also disclosed between DDC mRNA levels and TNM staging (P = .034). Univariate analysis showed that patients bearing DDC-positive tumors had a significantly decreased risk of death (hazard ratio = 0.23, P = .012) and local recurrence (hazard ratio = 0.32, P =.006), whereas DDC expression retained its favorable prognostic significance in the multivariate analysis. Kaplan-Meier curves further demonstrated that DDC-positive patients experienced longer overall and disease-free survival periods (P = .006 and P = .004, respectively). Moreover, DDC protein was detected in both neoplastic and noncancerous tissues. Therefore, our results suggest that DDC expression status could qualify as a promising biomarker for the future clinical management of laryngeal cancer patients.
L-DOPA 脱羧酶（DDC）在多巴胺的酶促合成中起着重要作用，其基因表达的改变已在几种恶性肿瘤中报道。我们的目的是分析喉组织中 DDC 信使 RNA（mRNA）和蛋白质的表达，并评估该分子在喉癌中的临床意义。在这项研究中，从 100 例喉癌患者手术切除的 157 个组织样本中分离出总 RNA。开发了一种基于 SYBR Green I 荧光染料的高度敏感实时聚合酶链反应方法，用于定量 DDC mRNA 水平。此外，还进行了 Western blot 分析以检测 DDC 蛋白。与非恶性对应物相比，原发性喉癌样本中 DDC mRNA 表达明显下调（P =.001）。还揭示了 DDC mRNA 水平与 TNM 分期之间存在显著负相关（P =.034）。单因素分析显示，携带 DDC 阳性肿瘤的患者死亡风险（危险比= 0.23，P =.012）和局部复发（危险比= 0.32，P =.006）显著降低，而 DDC 表达在多因素分析中仍保留其有利的预后意义。Kaplan-Meier 曲线进一步表明，DDC 阳性患者的总生存期和无病生存期更长（P =.006 和 P =.004）。此外，还在肿瘤和非癌组织中检测到了 DDC 蛋白。因此，我们的研究结果表明，DDC 表达状态可能成为未来喉癌患者临床管理的有前途的生物标志物。
