Expression of Tumor Necrosis Factor-alpha-induced Protein 8 in Pancreas Tissues and its Correlation with Epithelial Growth Factor Receptor Levels

  • Liu, Ke (Department of Hepatobiliary, Provincial Hospital affiliated to Shandong University) ;
  • Qin, Cheng-Kun (Department of Hepatobiliary, Provincial Hospital affiliated to Shandong University) ;
  • Wang, Zhi-Yi (Department of Hepatobiliary, Provincial Hospital affiliated to Shandong University) ;
  • Liu, Su-Xia (Department of immunology, Shandong University School of Medicine) ;
  • Cui, Xian-Ping (Department of Hepatobiliary, Provincial Hospital affiliated to Shandong University) ;
  • Zhang, Dong-Yuan (Department of Hepatobiliary, Provincial Hospital affiliated to Shandong University)
  • Published : 2012.03.31


Tumor necrosis factor (TNF)-alpha-induced protein 8 (TNFAIP8 or TIPE) is a recently identified protein considered to be associated with carcinogenesis. To investigate its expression pattern in pancreatic cancer patients and to analyse its correlation with clinicopathological significance and the expression levels of epithelial growth factor receptor (EGFR), immunohistochemistry was performed to detect the TNFAIP8 and EGFR proteins in pancreatic cancers, pancreatitis tissues, and healthy controls. The results showed stronger staining of TNFAIP8 protein in pancreatic cancer tissues compared with normal pancreas tissue. Furthermore, in 56 patients with pancreatic cancer, the expression levels of TNFAIP8 in patients with low tumor stage was higher than that with high tumor stage, and correlated with tumor staging and lymph node metastasis (P<0.05). Furthermore, TNFAIP8 expression positively correlated with EGFR levels (r=0.671135, P<0.05). These results indicate that TNFAIP8 may play important roles in the progression of pancreatic cancer.


  1. Aggarwal S, Gupta S, Gupta MK, et al (2011). Possible role of epidermal growth factor receptors in the therapy of pancreatic cancer. Crit Rev Ther Drug Carrier Syst, 28, 293-356.
  2. Azizi A, Naguib NN, Mbalisike E, et al (2011). Liver metastases of pancreatic cancer: role of repetitive transarterial chemoembolization (TACE) on tumor response and survival. Pancreas, 40, 1271-5.
  3. Dong QZ, Zhao Y, Liu Y, et al (2010). Overexpression of SCC-S2 correlates with lymph node metastasis and poor prognosis in patients with non-small-cell lung. Cancer Sci, 101, 1562-9.
  4. Freundt EC, Bidere N, Lenardo MJ (2008). A different TIPE of immune homeostasis. Cell, 133, 401-2.
  5. Hong SM, Park JY, Hruban RH, et al (2011). Molecular signatures of pancreatic cancer. Arch Pathol Lab Med, 135, 716-27.
  6. Ioannou N, Dalgleish AG, Seddon AM, et al (2011). Anti-tumour activity of afatinib, an irreversible ErbB family blocker, in human pancreatic tumour cells. Br J Cancer, 105, 1554-62.
  7. Kumar D, Whiteside TL, Kasid U (2000). Identification of a novel tumor necrosis factor-alpha-inducible gene, SCC-S2, containing the consensus sequence of a death effector domain of fas-associated death domain-like interleukin- 1beta-converting enzyme-inhibitory protein. J Biol Chem, 275, 2973-8.
  8. Kumar D, Gokhale P, Broustas C et al (2004). Expression of SCC-S2, a antiapoptotic molecule, correlates with enhanced proliferation antumorigenicity of MDA-MB 435 cells. Oncogene, 23, 612-6.
  9. Patel S, Wang FH, Whiteside TL, et al(1997). Identification of seven differentially displayed transcripts in human primary and matched metastatic head and neck squamous cell carcinoma cell lines: implications in metastasis and/or radiation response. Oral Oncol, 33, 197-203.
  10. Romanuik TL, Ueda T, Le N, et al (2009). Novel biomarkers for prostate cancer including noncoding transcripts. Am J Pathol, 175, 2264-76.
  11. Sharma C, Eltawil KM, Renfrew PD, et al (2011). Advances in diagnosis, treatment and palliation of pancreatic carcinoma: 1990-2010. World J Gastroenterol, 17, 867-97.
  12. Sun H, Gong S, Carmody RJ, et al (2008). TIPE2, a negative regulator of innate and adaptive immunity that maintains immune homeostasis. Cell, 133, 415-26.
  13. Vincent A, Herman J, Schulick R, et al (2011). Pancreatic cancer. Lancet, 378, 607-20.
  14. Xu S, Weihua Z (2011). Loss of EGFR induced autophagy sensitizes hormone refractory prostate cancer cells to adriamycin. Prostate, 71, 1216-24.
  15. You Z, Ouyang H, Lopatin D, et al (2001). Nuclear factorkappa B-inducible death effector domain-containing protein suppresses tumor necrosis factor-mediated apoptosis by inhibiting caspase-8 activity. J Biol Chem, 276, 26398-404.
  16. Zhang C, Chakravarty D, Sakabe I, et al (2006). Role of SCC-S2 in experimental metastasis and modulation of VEGFR-2, MMP-1, and MMP-9 expression. Mol Ther, 13, 947-55.

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