Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
권호 표지
DOI QR코드

DOI QR Code

Expression of Tumor Necrosis Factor Receptor-associated Factor 6 in Lung Cancer Tissues

  • Zhang, Xiu-Ling (Department of Pathology, First Affiliated Hospital, Guangxi Medical University) ;
  • Dang, Yi-Wu (Department of Pathology, First Affiliated Hospital, Guangxi Medical University) ;
  • Li, Ping (Department of Pathology, First Affiliated Hospital, Guangxi Medical University) ;
  • Rong, Min-Hua (Research Department, Affiliated Cancer Hospital, Guangxi Medical University) ;
  • Hou, Xin-Xi (Department of Pathology, First Affiliated Hospital, Guangxi Medical University) ;
  • Luo, Dian-Zhong (Department of Pathology, First Affiliated Hospital, Guangxi Medical University) ;
  • Chen, Gang (Department of Pathology, First Affiliated Hospital, Guangxi Medical University)
  • Published : 2015.01.22
Download PDF
⟨ Previous Next ⟩

Abstract

Background: Tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) has been reported to be associated with the development of various cancers. However, the role of TRAF6 in lung cancer remains unclear. Objective: To explore the expression and clinicopathological significance of TRAF6 protein in lung cancer tissues. Materials and Methods: Three hundred and sixty-five lung cancer samples and thirty normal lung tissues were constructed into 3 microarrays. The expression of TRAF6 protein was determined using immunohistochemistry (IHC). Furthermore, correlations between the expression of TRAF6 and clinicopathological parameters were investigated. Results: The expression of TRAF6 in total lung cancer tissues (365 cases), as well as in small cell lung cancer (SCLC, 26 cases) and non-small cell lung cancer (NSCLC, 339 cases) was significantly higher compared with that in normal lung tissues. The ROC curve showed that the area under curve of TRAF6 was 0.663 (95%CI 0.570~0.756) for lung cancer. The diagnostic sensitivity and specificity of TRAF6 were 52.6% and 80%, respectively. In addition, the expression of TRAF6 was correlated with clinical TNM stage, tumor size and lymph node metastasis in all lung cancers. Consistent correlations were also observed for NSCLCs. Conclusions: TRAF6 might be an oncogene and the expression of TRAF6 protein is related to the progression of lung cancer. Thus, TRAF6 might become a target for diagnosis and gene therapy for lung cancer patients.

Keywords

References

  1. Beroukhim R, Mermel CH, Porter D, et al (2010). The landscape of somatic copy-number alteration across human cancers. Nature, 463, 899-905. https://doi.org/10.1038/nature08822
  2. Brothers JF, Hijazi K, Mascaux C, et al (2013). Bridging the clinical gaps: genetic, epigenetic and transcriptomic biomarkers for the early detection of lung cancer in the post-National Lung Screening Trial era. BMC Med, 11, 168. https://doi.org/10.1186/1741-7015-11-168
  3. Chaudhry SI, Hooper S, Nye E, et al (2013). Autocrine IL-1beta-TRAF6 signalling promotes squamous cell carcinoma invasion through paracrine TNFalpha signalling to carcinoma-associated fibroblasts. Oncogene, 32, 747-58. https://doi.org/10.1038/onc.2012.91
  4. Chen G, Kronenberger P, Teugels E, et al (2012). Targeting the epidermal growth factor receptor in non-small cell lung cancer cells: the effect of combining RNA interference with tyrosine kinase inhibitors or cetuximab. BMC Med, 10, 28. https://doi.org/10.1186/1741-7015-10-28
  5. Chen G, Kronenberger P, Teugels E, et al (2013a). Effect of siRNAs targeting the EGFR T790M mutation in a non-small cell lung cancer cell line resistant to EGFR tyrosine kinase inhibitors and combination with various agents. Biochem Biophys Res Commun, 431, 623-9. https://doi.org/10.1016/j.bbrc.2012.12.070
  6. Chen G, Noor A, Kronenberger P, et al (2013b). Synergistic effect of afatinib with su11274 in non-small cell lung cancer cells resistant to gefitinib or erlotinib. PLoS One, 8, 59708. https://doi.org/10.1371/journal.pone.0059708
  7. Chen G, Umelo IA, Lv S, et al (2013c). miR-146a inhibits cell growth, cell migration and induces apoptosis in non-small cell lung cancer cells. PLoS One, 8, 60317. https://doi.org/10.1371/journal.pone.0060317
  8. Chen W, Zheng R, Zhang S, et al (2014). Annual report on status of cancer in China, 2010. Chin J Cancer Res, 26, 48-58.
  9. Elmetwali T, Young LS, Palmer DH (2010). CD40 ligand-induced carcinoma cell death: a balance between activation of TNFR-associated factor (TRAF) 3-dependent death signals and suppression of TRAF6-dependent survival signals. J Immunol, 184, 1111-20. https://doi.org/10.4049/jimmunol.0900528
  10. Gazala S, Pelletier JS, Storie D, et al (2013). A systematic review and meta-analysis to assess patient-reported outcomes after lung cancer surgery. Scientific World J, 2013, 789625.
  11. Granger CL, McDonald CF, Parry SM, et al (2013). Functional capacity, physical activity and muscle strength assessment of individuals with non-small cell lung cancer: a systematic review of instruments and their measurement properties. BMC Cancer, 13, 135. https://doi.org/10.1186/1471-2407-13-135
  12. Guo LJ, Liao L, Yang L, et al (2014). MiR-125a TNF receptor-associated factor 6 to inhibit osteoclastogenesis. Exp Cell Res, 321, 142-52. https://doi.org/10.1016/j.yexcr.2013.12.001
  13. Hirose T, Murata Y, Oki Y, et al (2012). Relationship of circulating tumor cells to the effectiveness of cytotoxic chemotherapy in patients with metastatic non-small-cell lung cancer. Oncol Res, 20, 131-7. https://doi.org/10.3727/096504012X13473664562583
  14. Ishida T, Mizushima S, Azuma S, et al (1996). Identification of TRAF6, a novel tumor necrosis factor receptor-associated factor protein that mediates signaling from an amino-terminal domain of the CD40 cytoplasmic region. J Biol Chem, 271: 28745-8. https://doi.org/10.1074/jbc.271.46.28745
  15. Jundi M, Nadiri A, Al-Zoobi L, et al (2012). CD40-mediated cell death requires TRAF6 recruitment. Immunobiology, 217, 375-83. https://doi.org/10.1016/j.imbio.2011.07.007
  16. Kim JL, Cho KH, Park EC, Cho WH (2014). A single measure of cancer burden combining incidence with mortality rates for worldwide application. Asian Pac J Cancer Prev, 15 433-9. https://doi.org/10.7314/APJCP.2014.15.1.433
  17. Kobayashi T, Walsh PT, Walsh MC, et al (2003). TRAF6 is a critical factor for dendritic cell maturation and development. Immunity, 19, 353-63. https://doi.org/10.1016/S1074-7613(03)00230-9
  18. Lee NK, Lee SY (2002). Modulation of life and death by the tumor necrosis factor receptor-associated factors (TRAFs). J Biochem Mol Biol, 35, 61-6. https://doi.org/10.5483/BMBRep.2002.35.1.061
  19. Liu H, Zhang T, Ye J, et al (2012). TNF receptor-associated factor 6 in advanced non-small cell lung cancer: clinical and prognostic implications. J Cancer Res Clin Oncol, 138, 1853-63. https://doi.org/10.1007/s00432-012-1255-6
  20. Meng Q, Zheng M, Liu H, et al (2012). TRAF6 regulates proliferation, apoptosis, and invasion of osteosarcoma cell. Mol Cell Biochem, 371: 177-186. https://doi.org/10.1007/s11010-012-1434-4
  21. Ramshankar V, Krishnamurthy A (2013). Lung cancer detection by screening - presenting circulating miRNAs as a promising next generation biomarker breakthrough. Asian Pac J Cancer Prev, 14, 2167-2172. https://doi.org/10.7314/APJCP.2013.14.4.2167
  22. Siegel R, Ma J, Zou Z, Jemal A (2014). Cancer statistics, 2014. CA Cancer J Clin, 64, 9-29. https://doi.org/10.3322/caac.21208
  23. Starczynowski DT, Lockwood WW, Delehouzee S, et al (2011). TRAF6 is an amplified oncogene bridging the RAS and NF-kappaB pathways in human lung cancer. J Clin Invest, 121, 4095-105. https://doi.org/10.1172/JCI58818
  24. Sun H, Li X, Fan L, et al (2014). TRAF6 is upregulated in colon cancer and promotes proliferation of colon cancer cells. Int J Biochem Cell Biol, 53, 195-201. https://doi.org/10.1016/j.biocel.2014.04.010
  25. Uribe P, Gonzalez S (2011). Epidermal growth factor receptor (EGFR) and squamous cell carcinoma of the skin: molecular bases for EGFR-targeted therapy. Pathol Res Pract, 207, 337-342. https://doi.org/10.1016/j.prp.2011.03.002
  26. Wang R, Wang G, Zhang N, et al (2013). Clinical evaluation and cost-effectiveness analysis of serum tumor markers in lung cancer. Biomed Res Int, 2013, 195692.
  27. Wang X, Ha T, Zou J, et al (2014). MicroRNA-125b protects against myocardial ischaemia/reperfusion injury via targeting p53-mediated apoptotic signalling and TRAF6. Cardiovasc Res, 102, 385-95. https://doi.org/10.1093/cvr/cvu044
  28. Xiao N, Li H, Luo J, et al (2012). Ubiquitin-specific protease 4 (USP4) targets TRAF2 and TRAF6 for deubiquitination and inhibits TNFalpha-induced cancer cell migration. Biochem J, 441, 979-86. https://doi.org/10.1042/BJ20111358
  29. Zapata JM, Krajewska M, Krajewski S, et al (2000). TNFR-associated factor family protein expression in normal tissues and lymphoid malignancies. J Immunol, 165, 5084-96. https://doi.org/10.4049/jimmunol.165.9.5084
  30. Zhong L, Cao F, You Q (2013). Effect of TRAF6 on the biological behavior of human lung adenocarcinoma cell. Tumour Biol, 34, 231-9. https://doi.org/10.1007/s13277-012-0543-8

Cited by

  1. Relationship between TRAF6 and deterioration of HCC: an immunohistochemical and in vitro study vol.16, pp.1, 2016, https://doi.org/10.1186/s12935-016-0352-z
  2. siRNA-induced TRAF6 knockdown promotes the apoptosis and inhibits the invasion of human lung cancer SPC-A1 cells vol.35, pp.4, 2016, https://doi.org/10.3892/or.2016.4602
  3. Cinchonine induces apoptosis of HeLa and A549 cells through targeting TRAF6 vol.36, pp.1, 2017, https://doi.org/10.1186/s13046-017-0502-8
  4. alkaloids to the RING domain of TRAF6 pp.1347-6947, 2018, https://doi.org/10.1080/09168451.2018.1559030