Expression of Cyclophilin A in Gastric Adenocarcinoma Patients and Its Inverse Association with Local Relapses and Distant Metastasis
- 175 Downloads
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.
KeywordsStomach cancer Two-dimensional gel electrophoresis Proteomics Mass spectrometry Cancer markers
- 2.Mizoue T, Yoshimura T, Tokui N, Hoshiyama Y, Yatsuya H, Sakata K, Kondo T, Kikuchi S, Toyoshima H, Hayakawa N, Tamakoshi A, Ohno Y, Fujino Y, Kaneko S (2003) Prospective study of screening for stomach cancer in Japan. Japan Collaborative Cohort Study Group Int J Cancer 106(1):103–107Google Scholar
- 16.Stepanov IV, Zavizlova MV, Grigor’eva ES, Bukurova YA, Afanas’ev SG, Cherdyntseva NV (2010) Clinico-morphological and genetics features of diffuse and intestinal gastric adenocarcinomas. Siberian journal of oncology 40:55–66 (in Russian)Google Scholar
- 27.Grigoryeva E, Bukurova Y, Cherdyntseva N, Afanasуev S, Komarova T, Rodicheva N, Beresten S (2009) 2Dproteomics of gastric cancer: identification of proteins with increased synthesis in tumor tissue. Siberian journal of oncology 5:37–42 (in Russian)Google Scholar
- 32.Howard BA, Zheng Z, Campa MJ, Wang MZ, Shama A, Haura E, Herndon JE II, Fitzgerald MC, Bepler G, Patz EF (2004) Translating biomarkers into clinical practice: prognostic implications of cyclophilin A and macrophage migratory inhibitory factor identified from protein expression profiles in non-small cell lung cancer. Lung Cancer 46:313–323PubMedCrossRefGoogle Scholar