Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Athens, Panepistimiopolis, 15701 Athens, Greece.
J Cancer Res Clin Oncol. 2013 Feb;139(2):297-306. doi: 10.1007/s00432-012-1326-8. Epub 2012 Oct 12.
Stomach adenocarcinoma represents a major health problem and is regarded as the second commonest cause of cancer-associated mortality, universally, since it is still difficult to be perceived at a curable stage. Several lines of evidence have pointed out that the expression of L-Dopa decarboxylase (DDC) gene and/or protein becomes distinctively modulated in several human neuroendocrine neoplasms as well as adenocarcinomas.
In order to elucidate the clinical role of DDC on primary gastric adenocarcinomas, we determined qualitatively and quantitatively the mRNA levels of the gene with regular PCR and real-time PCR by using the comparative threshold cycle method, correspondingly, and detected the expression of DDC protein by immunoblotting in cancerous and normal stomach tissue specimens.
A statistically significant association was disclosed between DDC expression and gastric intestinal histotype as well as tumor localization at the distal third part of the stomach (p = 0.025 and p = 0.029, respectively). Univariate and multivariate analyses highlighted the powerful prognostic importance of DDC in relation to disease-free survival and overall survival of gastric cancer patients. According to Kaplan-Meier curves, the relative risk of relapse was found to be decreased in DDC-positive (p = 0.031) patients who, also, exhibited higher overall survival rates (p = 0.016) than those with DDC-negative tumors.
This work is the first to shed light on the potential clinical usefulness of DDC, as an efficient tumor biomarker in gastric cancer. The provided evidence underlines the propitious predictive value of DDC expression in the survival of stomach adenocarcinoma patients.
胃腺癌是一个主要的健康问题,被认为是全球第二大常见的癌症相关死亡原因,因为它仍然很难在可治愈的阶段被察觉。有几条证据指出,L-多巴脱羧酶(DDC)基因和/或蛋白的表达在几种人类神经内分泌肿瘤以及腺癌中明显受到调节。
为了阐明 DDC 在原发性胃腺癌中的临床作用,我们使用常规 PCR 和实时 PCR 通过比较阈值循环法定性和定量地确定基因的 mRNA 水平,并通过免疫印迹检测癌组织和正常胃组织标本中 DDC 蛋白的表达。
DDC 表达与胃肠组织类型以及肿瘤在胃的远端三分之一部分的定位之间存在统计学显著关联(p=0.025 和 p=0.029)。单因素和多因素分析突出了 DDC 在胃癌患者无病生存率和总生存率方面的强大预后重要性。根据 Kaplan-Meier 曲线,DDC 阳性患者(p=0.031)的复发风险相对降低,而且这些患者的总生存率也更高(p=0.016)。
这项工作首次阐明了 DDC 作为胃癌有效肿瘤标志物的潜在临床用途。提供的证据强调了 DDC 表达对胃腺癌患者生存的有利预测价值。