ABSTRACT
BACKGROUND: Claudin, occludin, and zonula occludens (ZO)-1 are known as tight-junction-associated proteins. The aim of this study was to examine the expression of these proteins in gastric carcinoma. METHODS: Gastric cancer tissues (n = 124) were obtained from 124 patients who underwent gastrectomy at our hospital between January 2000 and December 2004. The expression of the above tight-junction-associated proteins in carcinoma, normal mucosa, and metaplastic epithelium was examined using immunohistochemistry. In addition, the expression of claudin-4 mRNA was examined in fresh frozen tissue obtained from 34 patients. RESULTS: Significant correlations were seen between the expression of claudin-4, occludin, and ZO-1. In regard to claudin-4, significant correlations were seen between the expression of claudin-4 evaluated by immunohistochemistry and the expression of claudin-4 mRNA. Claudin-4 expression was significantly decreased in tumors with undifferentiated-type adenocarcinoma, advanced T stage, lymph node metastasis, and peritoneal metastasis. Occludin and ZO-1 expression was significantly decreased in tumors with undifferentiated-type adenocarcinoma. Overall survival was significantly shorter in patients with low claudin-4 expression. Cox multivariate analysis revealed that low claudin-4 expression was independently associated with significantly decreased overall survival. CONCLUSION: Tight-junction-associated proteins, particularly claudin-4, may play important roles in determining invasiveness, metastatic potential, and survival in gastric cancer.
Subject(s)
Adenocarcinoma/metabolism , Adenocarcinoma/mortality , Biomarkers, Tumor/metabolism , Membrane Proteins/metabolism , Stomach Neoplasms/metabolism , Stomach Neoplasms/mortality , Adenocarcinoma/secondary , Adolescent , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/genetics , Claudin-4 , Down-Regulation , Female , Gene Expression Regulation, Neoplastic , Humans , Immunoenzyme Techniques , Lymphatic Metastasis , Male , Membrane Proteins/genetics , Middle Aged , Neoplasm Staging , Prognosis , RNA, Messenger/genetics , RNA, Messenger/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Stomach Neoplasms/pathology , Survival Rate , Tissue Array Analysis , Young AdultABSTRACT
Ornithine decarboxylase (ODC) is a key enzyme in the biosynthesis of polyamines, which are essential for cell proliferation. ODC activity was measured in 47 colorectal cancer patients, 5 patients with adenoma of colorectum and 4 healthy volunteers. Mean ODC activities of cancer tissue, non-cancerous mucosa from cancer-bearing colorectum, adenoma tissue, and normal mucosa from healthy volunteers were 435+/-392, 154+/-173, 295+/-202, 103+/-60 pmol CO2/h/mg protein, respectively. ODC activity of cancer tissue or adenoma tissue was significantly higher than that of the others. Among colorectal cancer patients, ODC activity in cancer tissue was correlated with T factors, lymph node metastasis and stages. Patients with tumors that had high ODC activity (> or =350 pmol CO2/h/mg protein) showed a poor 10-year survival rate. These results suggest that ODC activity may be a useful marker for patients' prognosis after surgery.
