Advertisement

Pathology & Oncology Research

, Volume 20, Issue 2, pp 467–473 | Cite as

Expression of Cyclophilin A in Gastric Adenocarcinoma Patients and Its Inverse Association with Local Relapses and Distant Metastasis

  • Evgeniya S. Grigoryeva
  • Nadezhda V. Cherdyntseva
  • Mikhail S. Karbyshev
  • Viktor V. Volkomorov
  • Ivan V. Stepanov
  • Marina V. Zavyalova
  • Vladimir M. Perelmuter
  • Mikhail A. Buldakov
  • Sergey G. Afanasjev
  • Sergey A. Tuzikov
  • Yulia A. Bukurova
  • Nikolai A. Lisitsyn
  • Sergey F. Beresten
Research

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.

Keywords

Stomach cancer Two-dimensional gel electrophoresis Proteomics Mass spectrometry Cancer markers 

References

  1. 1.
    Jemal A, Center M, DeSantis C, Ward E (2010) Global patterns of cancer incidence and mortality rates and trends. Cancer Epidemiol Biomarkers Prev 19(8):1893–1907PubMedCrossRefGoogle Scholar
  2. 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
  3. 3.
    Washington K (2010) 7th Edition of the AJCC Cancer Staging Manual: Stomach. Ann Surg Oncol 17:3077–3079PubMedCrossRefGoogle Scholar
  4. 4.
    Volkomorov V, Grigoryeva E, Krasnov G, Litviakov N, Tsyganov M, Karbyshev M, Zavyalova M, Afanasуev S, Cherdyntseva N, Lisitsyn N, Beresten S (2013) Search for potential gastric cancer markers using miRNA databases and gene expression analysis. Exp Oncol 35(1):2–7PubMedGoogle Scholar
  5. 5.
    Obchoei S, Weakley SM, Wongkham S, Wongkham C, Sawanyawisuth K, Yao Q, Chen C (2011) Cyclophilin A enhances cell proliferation and tumor growth of liver fluke-associated cholangiocarcinoma. Mol Cancer 10:102PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Nigro P, Satoh K, O’Dell M, Soe N, Cui Z, Mohan A, Abe J, Alexis J, Sparks J, Berk B (2011) Cyclophilin A is an inflammatory mediator that promotes atherosclerosis in apolipoprotein E-deficient mice. J Exp Med 208(1):53–66PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.
    Lee J (2010) Role of Cyclophilin A during Oncogenesis. Arch Pharm Res 33:181–187PubMedCrossRefGoogle Scholar
  8. 8.
    Campa MJ, Wang MZ, Howard B, Fitzgerald MC, Patz EF (2003) Protein expression profiling identifies macrophage migration inhibitory factor and cyclophilin A as potential molecular targets in nonsmall-cell lung cancer. Cancer Res 63:1652–1656PubMedGoogle Scholar
  9. 9.
    Cecconi D, Astner H, Donadelli M, Palmieri M, Missiaglia E, Hamdan M, Scarpa A, Righetti PG (2003) Proteomic analysis of pancreatic ductal carcinoma cells treated with 5-aza-2′-deoxycytidine. Electrophoresis 24:4291–4303PubMedCrossRefGoogle Scholar
  10. 10.
    Lim SO, Park SJ, Kim W, Park SG, Kim HJ, Kim YI, Sohn TS, Noh JH, Jung G (2002) Proteome analysis of hepatocellular carcinoma. Biochem Biophys Res Commun 291:1031–1037PubMedCrossRefGoogle Scholar
  11. 11.
    Yang J, Li A, Yang Y, Li X (2011) Identification of cyclophilin A as a potential prognostic factor for clear-cell renal cell carcinoma by comparative proteomic analysis. Cancer Biol Ther 11(5):535–546PubMedCrossRefGoogle Scholar
  12. 12.
    Zheng J, Koblinski JE, Dutson LV, Feeney YB, Clevenger CV (2008) Prolyl isomerase cyclophilin A regulation of Janus-activated kinase 2 and the progression of human breast cancer. Cancer Res 68:7769–7778PubMedCrossRefGoogle Scholar
  13. 13.
    Hathout Y, Riordan K, Gehrmann M, Fenselau C (2002) Differential protein expression in the cytosol fraction of an MCF-7 breast cancer cell line selected for resistance toward melphalan. J Proteome Res 1:435–442PubMedCrossRefGoogle Scholar
  14. 14.
    Krasnov GS, Oparina NY, Hankin SL, Mashkova TD, Ershov AN, Zatsepina OG, Karpov VL, Beresten SF (2009) Identification of proteins with altered expression in colorectal cancer by means of 2D-proteomics. Mol Biol (Mosk) 43:321–328CrossRefGoogle Scholar
  15. 15.
    Mortz E, Krogh T, Vorum H, Gоrg A (2001) Improved silver staining protocols for high sensitivity protein identification using matrix-assisted laser desorption/ionization-time of flight analysis. Proteomics 1:1359–1363PubMedCrossRefGoogle Scholar
  16. 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
  17. 17.
    El-Rifai W, Moskaluk CA, Abdrabbo MK, Harper J, Yoshida C, Riggins GJ, Frierson HF Jr, Powell SM (2002) Gastric Cancers Over express S100A Calcium-binding Proteins. Cancer Research 62:6823–6826PubMedGoogle Scholar
  18. 18.
    Oien KA, Vass KJ, Downie I, Fullarton G, Keith NW (2003) Profiling, comparison and validation of gene expression in gastric carcinoma and normal stomach. Oncogene 22:4287–4300PubMedCrossRefGoogle Scholar
  19. 19.
    Ikeguchia M, Fukudaa K, Okaa S, Yamaguchia K, Hisamitsua K, Tsujitania S, Sakatanib T, Uedac T, Kaibaraa N (2001) Clinicopathological Significance of Cathepsin D Expression in Gastric Adenocarcinoma. Oncology 61:71–78CrossRefGoogle Scholar
  20. 20.
    Sribenja S, Li M, Wongkham S, Wongkham C, Yao Q, Chen C (2009) Advances in thymosin beta10 research: differential expression, molecular mechanisms, and clinical implications in cancer and other conditions. Cancer Invest 27(10):1016–1022PubMedCrossRefGoogle Scholar
  21. 21.
    Liaudet-Coopman E, Beaujouin M, Derocq D, Garcia M, Glondu-Lassis M, Laurent-Matha V, Prébois C, Rochefort H, Vignon F (2006) Cathepsin D: newly discovered functions of a long-standing aspartic protease in cancer and apoptosis. Cancer Lett 237(2):167–179PubMedCrossRefGoogle Scholar
  22. 22.
    Salama I, Malone PS, Mihaimeed F, Jones JL (2008) A review of the S100 proteins in cancer. Eur J Surg Oncol 34(4):357–364PubMedCrossRefGoogle Scholar
  23. 23.
    Adachi Y, Yasuda K, Inomata M, Sato K, Shiraishi N, Kitano S (2000) Pathology and prognosis of gastric carcinoma: well versus poorly differentiated type. Cancer 89:1418–1424PubMedCrossRefGoogle Scholar
  24. 24.
    Kim JP, Lee JH, Kim SJ, Yu HJ, Yang HK (1998) Clinicopathologic characteristics and prognostic factors in 10783 patients with gastric cancer. Gastric Cancer 1:125–133PubMedCrossRefGoogle Scholar
  25. 25.
    Yoshihara T, Kadota Y, Yoshimura Y, Tatano Y, Takeuchi N, Okitsu H, Umemoto A, Yamauchi T, Itoh K (2006) Proteomic alteration in gastic adenocarcinomas from Japanese patients. Molecular Cancer 5:75PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    Li Z, Zhao X, Bai S, Wang Z, Chen L, Wei Y, Huang C (2008) Proteomics Identification of Cyclophilin A as a Potential Prognostic Factor and Therapeutic Target in Endometrial Carcinoma. Mol Cell Proteomics 7:1810–1823PubMedCrossRefGoogle Scholar
  27. 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
  28. 28.
    Ryu JW, Kim HJ, Lee YS, Myong NH, Hwang CH, Lee GS, Yom HC (2003) The proteomics approach to find biomarkers in gastric cancer. J Korean Med Sci 18(4):505–509PubMedCentralPubMedGoogle Scholar
  29. 29.
    Bai Z, Ye Y, Liang B, Xu F, Zhang H, Zhang Y, Peng J, Shen D, Cui Z, Zhang Z, Wang S (2011) Proteomics-based identification of a group of apoptosis-related proteins and biomarkers in gastric cancer. Int J Oncol 38(2):375–383PubMedGoogle Scholar
  30. 30.
    Choi KJ, Piao YJ, Lim MJ, Kim JH, Ha J, Choe W, Kim SS (2007) Overexpressed cyclophilin A in cancer cells renders resistance to hypoxia- and cisplatin-induced cell death. Cancer Res 67:3654–3662PubMedCrossRefGoogle Scholar
  31. 31.
    Qi YJ, He QY, Ma YF, Du YW, Liu GC, Li YJ, Tsao GS, Ngai SM, Chiu JF (2008) Proteomic identification of malignant transformation-related proteins in esophageal squamous cell carcinoma. J Cell Biochem 104:1625–1635PubMedCrossRefGoogle Scholar
  32. 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

Copyright information

© Arányi Lajos Foundation 2013

Authors and Affiliations

  • Evgeniya S. Grigoryeva
    • 1
    • 5
  • Nadezhda V. Cherdyntseva
    • 1
  • Mikhail S. Karbyshev
    • 1
    • 4
  • Viktor V. Volkomorov
    • 1
  • Ivan V. Stepanov
    • 2
  • Marina V. Zavyalova
    • 2
  • Vladimir M. Perelmuter
    • 1
  • Mikhail A. Buldakov
    • 1
  • Sergey G. Afanasjev
    • 1
  • Sergey A. Tuzikov
    • 1
  • Yulia A. Bukurova
    • 3
  • Nikolai A. Lisitsyn
    • 3
  • Sergey F. Beresten
    • 3
  1. 1.Cancer Research Institute of Siberian Branch of RAMSTomskRussian Federation
  2. 2.Siberian State Medical UniversityTomskRussian Federation
  3. 3.Engelhardt Institute of Molecular BiologyRussian Academy of SciencesMoscowRussian Federation
  4. 4.International Biotechnology Center “Generium”MoscowRussian Federation
  5. 5.TomskRussia

Personalised recommendations