l-Dopa decarboxylase (DDC) constitutes an emerging biomarker in predicting patients’ survival with stomach adenocarcinomas

• Published in: Journal of cancer research and clinical oncology Vol. 139; no. 2; pp. 297 - 306
• Main Authors: Florou, Dimitra, Papadopoulos, Iordanis N., Fragoulis, Emmanuel G., Scorilas, Andreas
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01-02-2013; Springer; Springer Nature B.V
• Subjects: Adenocarcinoma - genetics; Adenocarcinoma - mortality; Adenocarcinoma - pathology; Adult; Aged; Aged, 80 and over; Antineoplastic agents; Biological and medical sciences; Biomarkers; Biomarkers, Tumor - genetics; Cancer Research; Dopa Decarboxylase - genetics; Female; Gastric cancer; Gastric Mucosa - metabolism; Gastric Mucosa - pathology; Gastroenterology. Liver. Pancreas. Abdomen; Gene Expression; Hematology; Humans; Internal Medicine; Male; Medical prognosis; Medical sciences; Medicine; Medicine & Public Health; Middle Aged; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Neoplasm Grading; Neoplasm Staging; Oncology; Original Paper; Pharmacology. Drug treatments; Prognosis; Stomach Neoplasms - genetics; Stomach Neoplasms - mortality; Stomach Neoplasms - pathology; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumors; Molecular tumor marker; Prognosis; Dopa decarboxylase; Real-time PCR; Gastric cancer; Western blotting; Agonist; RNA-directed DNA polymerase; Genetic marker; Zalcitabine; Biological marker; Lyases; Tumoral marker; Molecular marker; Stomach cancer; Carboxy-lyases; Reverse transcriptase inhibitor; Immunoblotting assay; Nucleoside analog; Levodopa; L-Dopa decarboxylase; Pyrimidine nucleoside; Gastric disease; Human; Enzyme; Transferases; Prediction; Enzyme inhibitor; Patient; Malignant tumor; Stomach adenocarcinoma; Real time; Survival; Polymerase chain reaction; Carbon-carbon lyases; Nucleotidyltransferases; D2 Dopamine receptor; Dideoxynucleoside; Digestive diseases; Aromatic-L-amino-acid decarboxylase; Molecular biology; Cancer
• ISSN: 0171-5216; 1432-1335
• DOI: 10.1007/s00432-012-1326-8

Purpose
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.
Methods
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.
Results
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.
Conclusions
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.