ABSTRACT
The aim of this study was to identify new protein markers of the intestinal and diffuse type gastric adenocarcinoma and to determine their relation to local relapses and distant metastasis. Using two-dimensional gel electrophoresis, we searched for proteins that are overexpressed in the intestinal and/or diffuse type gastric adenocarcinoma, as compared to matched normal mucosa samples with further change confirmation by Western blot. Expression of the selected proteins was further assessed by immunohistocemistry in a large panel of gastric adenocarcinoma with various clinicopathological features. Expression level of cyclophilin A measured with western blot appeared to be increased on average ten times in 63 % of gastric adenocarcinoma vs. paired samples of normal mucosa. The frequency of immunihistochemistry detected cyclophilin A protein expression was found to be equal in tumor of both histotypes, but staining intensity was higher in intestinal versus diffuse types of gastric adenocarcinoma. cyclophilin A protein expression appeared to be lower in deeply invading glandular and cribriform structures of intestinal tumors, as well as in discretely placed groups of the intestinal tumor cells. Local relapses as well as distant metastases registered within 3 year follow up were observed to occur much less frequently in patients with positive cyclophilin A immunostaining in gastric tumors. Analysis of cyclophilin A expression has a potential value for prognosis of gastric adenocarcinoma recurrence and distant metastasis.
Subject(s)
Adenocarcinoma/metabolism , Adenocarcinoma/pathology , Cyclophilin A/metabolism , Neoplasm Metastasis/pathology , Neoplasm Recurrence, Local/metabolism , Stomach Neoplasms/metabolism , Stomach Neoplasms/pathology , Biomarkers, Tumor/metabolism , Female , Gastric Mucosa/metabolism , Gastric Mucosa/pathology , Humans , Immunohistochemistry/methods , Intestinal Neoplasms/metabolism , Intestinal Neoplasms/pathology , Male , Middle Aged , Neoplasm Recurrence, Local/pathology , Neoplasm Staging/methods , PrognosisABSTRACT
Microbes living in the mammalian gut exist in constant contact with immunity system that prevents infection and maintains homeostasis. Enteric alpha defensins play an important role in regulation of bacterial colonization of the gut, as well as in activation of pro- and anti-inflammatory responses of the adaptive immune system cells in lamina propria. This review summarizes currently available data on functions of mammalian enteric alpha defensins in the immune defense and changes in their secretion in intestinal inflammatory diseases and cancer.
