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Clinical Significance of Expression and Amplification of the DcR3 Gene in Pancreatic Carcinomas

  • Zhou, Jian (Department of General Surgery, the First Affiliated Hospital of Soochow University) ;
  • Song, Shi-Duo (Department of General Surgery, the First Affiliated Hospital of Soochow University) ;
  • Li, De-Chun (Department of General Surgery, the First Affiliated Hospital of Soochow University) ;
  • Zhou, Jin (Department of General Surgery, the First Affiliated Hospital of Soochow University) ;
  • Zhu, Dong-Ming (Department of General Surgery, the First Affiliated Hospital of Soochow University) ;
  • Zheng, Shi-Ying (Department of Cardio-Thoracic Surgery, the First Affiliated Hospital of Soochow University)
  • Published : 2012.02.29

Abstract

This study aimed to investigate the clinical significance of expression and amplification of decoy receptor 3 (DcR3) in pancreatic carcinomas (PC). mRNA expression was detected by PQ-PCR, and amplification was determined. DcR3 protein expression was detected by immunohistochemistry and ELISA. Correlations between DcR3 expression and clinical pathological factors were analyzed. The relative amount of DcR3 in PC tissues and non-cancerous tissues showed a statistically significant difference, 21 cases displaying more than two fold DcR3 amplification, while no such amplification was found in normal pancreatic tissues. DcR3 positive cell staining was located in the cytoplasm. The positive rate of DcR3 in PC and non-cancerous tissues showed a significant difference. DcR3 mRNA expression was correlated with clinical staging, size of the tumor, lymph node metastasis and histological staging, while protein expression was correlated with clinical data like tumor size. DcR3 gene amplification only correlated with tumor size. The level of DcR3 in serum of the PC resectable group before operation was $72.2{\pm}10.2$ pg/ml, showing a significant difference compared to gallbladder carcinoma group (GC) or pancreatic benign tumor (PBT) group (P < 0.01). In conclusion, DcR3 amplification is correlated with DcR3 expression in PC tissues, especially those clinical pathological factors which reflect tumor progression. Assessment of DcR3 level in sera of PC patients may be helpful for the early diagnosis and prognostic judgement.

Keywords

References

  1. Anderson GL, McIntosh M, Wu L, et al (2010). Assessing lead time of selected ovarian cancer biomarkers. a nested casecontrol study. J Natl Cancer Inst, 102, 26-38. https://doi.org/10.1093/jnci/djp438
  2. Arakawa Y, Tachibana O, Hasegawa M, et al (2005). Frequent gene amplification and overexpression of decoy receptor 3 in glioblastoma. Acta Neuropathol, 109, 294-8. https://doi.org/10.1007/s00401-004-0956-6
  3. Bai C, Connolly B, Metzker ML, et al (2000). Overexpression of M68/DcR3 in human gastrointestinal tract tumors independent of gene amplification and its location in a fourgene cluster. Proc Natl Acad Sci, 97, 1230-5. https://doi.org/10.1073/pnas.97.3.1230
  4. Bamias G, Siakavellas SI, Stamatelopoulos KS, et al (2008). Circulating levels of TNF-like cytokine 1A (TL1A) and its decoy receptor 3 (DcR3) in rheumatoid arthritis. Clin Immunol, 129, 249-55. https://doi.org/10.1016/j.clim.2008.07.014
  5. Chen G, Luo D (2008). Expression of decoy receptor 3 in liver tissue microarrays. Natl Med J India, 21, 275-8.
  6. Chen G, Luo DZ, Wang Y (2007). Relationship between expression of decoy receptor 3 and apoptosis in hepatocellular carcinoma. Zhonghua Binglixue Zazhi, 36, 113-7.
  7. Chen L, Tian X, Li W, et al (2009). Expressions of Fas/DcR3 and RGD-FasL mediated apoptosis in pituitary adenomas. Neurol India, 57, 28-30. https://doi.org/10.4103/0028-3886.48808
  8. Connor JP, Felder M (2008). Ascites from epithelial ovarian cancer contain high levels of functional decoy receptor 3 (DcR3) and is associated with platinum resistance. Gynecol Oncol, 111, 330-5. https://doi.org/10.1016/j.ygyno.2008.07.012
  9. Gill RM, Hunt JS (2004). Soluble receptor (DcR3) and cellular inhibitor of apoptosis-2 (cIAP-2) protect human cytotrophoblast cells against LIGHT-mediated apoptosis. Am J Pathol, 165, 309-17. https://doi.org/10.1016/S0002-9440(10)63298-1
  10. Hsu TL, Wu YY, Chang YC, et al (2005). Attenuation of Th1 response in decoy receptor 3 transgenic mice. J Immunol, 175, 5135-45. https://doi.org/10.4049/jimmunol.175.8.5135
  11. Li H, Zhang L, Lou H, et al (2005). Overexpression of decoy receptor 3 in precancerous lesions and adenocarcinoma of the esophagus. Am J Clin Pathol, 124, 282-7. https://doi.org/10.1309/XK594E4B5WU82QR6
  12. Li W, Zhang C, Chen C, et al (2007). Correlation between expression of DcR3 on tumor cells and sensitivity to FasL. Cell Mol Immunol, 4, 455-60.
  13. Longley DB, Allen WL, McDermott U, et al (2004). The roles of thymidylate synthase and p53 in regulating Fas-mediated apoptpsis in response to antimeabolites, 10, 3562-71. https://doi.org/10.1158/1078-0432.CCR-03-0532
  14. Macher-Goeppinger S, Aulmann S, Wagener N, et al (2008). Decoy receptor 3 is a prognostic factor in renal cell cancer. Neoplasia, 10, 1049-56. https://doi.org/10.1593/neo.08626
  15. Mueller AM, Pedre X, Killian S, et al (2009). The Decoy Receptor 3 (DcR3, TNFRSF6B) suppresses Th17 immune responses and is abundant in human cerebrospinal fluid. J Neuroimmunol, 209, 57-64. https://doi.org/10.1016/j.jneuroim.2009.01.024
  16. Ohshima K, Haraoka S, Sugihara M, et al (2000). Amplification and expression of a decoy receptor for Fas ligand (DcR3) in virus (EBV or HTLV-I) associated lymphomas. Cancer letters, 160, 89-97. https://doi.org/10.1016/S0304-3835(00)00567-X
  17. Pitti RM, Marsters SA, Lawrence DA, et al (1998). Genomic amplification of a decoy receptor for Fas ligand in lung and colon cancer. Nature, 396, 699-703. https://doi.org/10.1038/25387
  18. Schwendel A, Richard F, Langreck H, et al (1998). Chromosome alterations in breast cancer carcinomas. frequent involvement of DNA losses including chromosomes 4q and 21q. Br J cancer, 78, 806-11. https://doi.org/10.1038/bjc.1998.583
  19. Shen HW, Gao SL, Wu YL, et al (2005). Overexpression of decoy receptor 3 in hepatocellular carcinoma and its association with resistance to Fas ligand-mediated apoptosis. World J Gastroenterol, 11, 5926-30. https://doi.org/10.3748/wjg.v11.i38.5926
  20. Shi G, Wu Y, Zhang J, Wu J (2003). Death decoy receptor TR6/ DcR3 inhibits T cell chemotaxis in vitro and in vivo. J Immunol, 171, 3407-14. https://doi.org/10.4049/jimmunol.171.7.3407
  21. Takahama Y, Yamada Y, Emoto K (2002). The prognostic significance of overexpression of the decoy receptor for Fas ligand (DcR3) in patients with gastric carcinomas. Gastric Cancer, 5, 61-8. https://doi.org/10.1007/s101200200011
  22. Wu Y, Han B, Sheng H, et al (2003). Clinical significance of detecting elevated serum DcR3/TR6/M68 in malignant tumor patients. Int J Cancer, 105, 724-32. https://doi.org/10.1002/ijc.11138
  23. Yang CR, Hsieh SL, Teng CM, et al (2004). Soluble decoy receptor 3 induces angiogenesis by neutralization of TL1A, a cytokine belonging to tumor necrosis factor superfamily and exhibiting angiostatic action. Cancer Res, 64, 1122-9. https://doi.org/10.1158/0008-5472.CAN-03-0609
  24. You RI, Chang YC, Chen PM, et al (2008). Apoptosis of dendritic cell induced by decoy receptor 3(DcR3). Blood, 111, 1480-8.

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