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Meta-analysis of Associations of the Ezrin Gene with Human Osteosarcoma Response to Chemotherapy and Prognosis

  • Wang, Zhe (Graduate School of Guangxi Medical University) ;
  • He, Mao-Lin (Division of Spinal Surgery, The First Affiliated Hospital of Guangxi Medical University) ;
  • Zhao, Jin-Min (Department of Orthopedic Trauma and Hand Surgery, The First Affiliated Hospital of Guangxi Medical University) ;
  • Qing, Hai-Hui (Graduate School of Guangxi Medical University) ;
  • Wu, Yang (Graduate School of Guangxi Medical University)
  • Published : 2013.05.30

Abstract

Various studies examining the relationship between Ezrin overexpression and response to chemotherapy and clinical outcome in patients with osteosarcoma have yielded inconclusive results. We accordingly conducted a meta-analysis of 7 studies (n = 318 patients) that evaluated the correlation between Ezrin and histologic response to chemotherapy and clinical prognosis (death). Data were synthesized in receiver operating characteristic curves and with fixed-effects and random-effects likelihood ratios and risk ratios. Quantitative synthesis showed that Ezrin is not a prognostic factor for the response to chemotherapy. The positive likelihood ratio was 0.538 (95% confidence interval [95% CI], 0.296- 0.979; random-effects calculation), and the negative likelihood ratio was 2.151 (95% CI, 0.905- 5.114; random-effects calculations). There was some between-study heterogeneity, but no study showed strong discriminating ability. Conversely, Ezrin positive status tended to be associated with a lower 2-year survival (risk ratio, 2.45; 95% CI, 1.26-4.76; random-effects calculation) with some between-study heterogeneity that disappeared when only studies that employed immunohistochemistry were considered (risk ratio, 2.97; 95% CI, 2.01- 4.40; fixed-effects calculation). To conclude, Ezrin is not associated with the histologic response to chemotherapy in patients with osteosarcoma, whereas Ezrin positivity was associated with a lower 2-year survival rate regarding risk of death at 2 years. Expression change of Ezrin is an independent prognostic factor in patients with osteosarcoma.

Keywords

Ezrin;osteosarcoma;chemotherapy;survival;meta-analysis

References

  1. Bal N, Yildirim S, Nursal TZ, Bolat F, Kayaselcuk F (2007). Association of ezrin expression in intestinal and diffuse gastric carcinoma with clinicopathological parameters and tumor type. World J Gastroenterol, 13, 3726-9.
  2. Boldrini E, Peres SV, Morini S, de Camargo B (2010). Immunoexpression of Ezrin and CD44 in patients with osteosarcoma. J Pediatr Hematol Oncol, 32, e213-7. https://doi.org/10.1097/MPH.0b013e3181e5e247
  3. Brambilla D, Fais S (2009). The Janus-faced role of ezrin in “linking” cells to either normal or metastatic phenotype. Int J Cancer, 125, 2239-45. https://doi.org/10.1002/ijc.24734
  4. Bretscher A, Edwards K, Fehon RG (2002). ERM proteins and merlin: integrators at the cell cortex. Nat Rev Mol Cell Biol, 3, 586-99. https://doi.org/10.1038/nrm882
  5. Elliott BE, Meens JA, SenGupta SK, Louvard D, Arpin M (2005). The membrane cytoskeletal crosslinker ezrin is required for metastasis of breast carcinoma cells. Breast Cancer Res, 7, R365-73. https://doi.org/10.1186/bcr1006
  6. Federici C, Brambilla D, Lozupone F, et al (2009). Pleiotropic function of ezrin in human metastatic melanomas. Int J Cancer, 124, 2804-12. https://doi.org/10.1002/ijc.24255
  7. Foster L, Dall GF, Reid R, Wallace WH, Porter DE (2007). Twentieth-century survival from osteosarcoma in childhood. Trends from 1933 to 2004. J Bone Joint Surg Br, 89, 1234-8.
  8. Gautreau A, Poullet P, Louvard D, Arpin M (1999). Ezrin, a plasma membrane-microfilament linker, signals cell survival through the phosphatidylinositol 3-kinase/Akt pathway. Proc Natl Acad Sci U S A, 96, 7300-5. https://doi.org/10.1073/pnas.96.13.7300
  9. Gorlick R (2009). Current concepts on the molecular biology of osteosarcoma. Cancer Treat Res, 152, 467-78. https://doi.org/10.1007/978-1-4419-0284-9_27
  10. Hong-Jian W, Cheng-Zhang S, Xian-Feng Q, Qiu-Shi H (2007). Expression of ezrin, E-cadherin and focal adhesion kinase in colorectal carcinoma and their clinical significances. World Chin J Digestol, 15, 5.
  11. Hunter KW (2004). Ezrin, a key component in tumor metastasis. Trends Mol Med, 10, 201-4. https://doi.org/10.1016/j.molmed.2004.03.001
  12. Khanna C, Wan X, Bose S, et al (2004). The membrane-cytoskeleton linker ezrin is necessary for osteosarcoma metastasis. Nat Med, 10, 182-6. https://doi.org/10.1038/nm982
  13. Kim C, Shin E, Hong S, et al (2009). Clinical value of ezrin expression in primary osteosarcoma. Cancer Res Treat, 41, 138-44. https://doi.org/10.4143/crt.2009.41.3.138
  14. Kim MS, Song WS, Cho WH, Lee SY, Jeon DG (2007). Ezrin expression predicts survival in stage IIB osteosarcomas. Clin Orthop Relat Res, 459, 229-36. https://doi.org/10.1097/BLO.0b013e3180413dbf
  15. Krishnan K, Bruce B, Hewitt S, et al (2006). Ezrin mediates growth and survival in Ewing's sarcoma through the AKT/mTOR, but not the MAPK, signaling pathway. Clin Exp Metastasis, 23, 227-36. https://doi.org/10.1007/s10585-006-9033-y
  16. Kumar R, Wang RA, Bagheri-Yarmand R (2003). Emerging roles of MTA family members in human cancers. Semin Oncol, 30, 30-7. https://doi.org/10.1053/sonc.2003.37273
  17. Lau J, Ioannidis JP, Schmid CH (1997). Quantitative synthesis in systematic reviews. Ann Intern Med, 127, 820-6. https://doi.org/10.7326/0003-4819-127-9-199711010-00008
  18. Li YG, Geng X (2010). A meta-analysis on the association of HER-2 overexpression with prognosis in human osteosarcoma. Eur J Cancer Care (Engl), 19, 313-6. https://doi.org/10.1111/j.1365-2354.2008.00970.x
  19. Martin TA, Harrison G, Mansel RE, Jiang WG (2003). The role of the CD44/ezrin complex in cancer metastasis. Crit Rev Oncol Hematol, 46, 165-86. https://doi.org/10.1016/S1040-8428(02)00172-5
  20. McClatchey AI (2003). Merlin and ERM proteins: unappreciated roles in cancer development? Nat Rev Cancer, 3, 877-83. https://doi.org/10.1038/nrc1213
  21. Moses LE, Shapiro D, Littenberg B (1993). Combining independent studies of a diagnostic test into a summary ROC curve: dataanalytic approaches and some additional considerations. Stat Med, 12, 1293-316. https://doi.org/10.1002/sim.4780121403
  22. Ottaviani G, Jaffe N (2009). The etiology of osteosarcoma. Cancer Treat Res, 152, 15-32. https://doi.org/10.1007/978-1-4419-0284-9_2
  23. Pakos EE,Ioannidis JP (2003). The association of P-glycoprotein with response to chemotherapy and clinical outcome in patients with osteosarcoma. A meta-analysis. Cancer, 98, 581-9. https://doi.org/10.1002/cncr.11546
  24. Pakos EE, Kyzas PA, Ioannidis JP (2004). Prognostic significance of TP53 tumor suppressor gene expression and mutations in human osteosarcoma: a meta-analysis. Clin Cancer Res, 10, 6208-14. https://doi.org/10.1158/1078-0432.CCR-04-0246
  25. Petitti DB (2000). Meta-analysis, decision analysis, and costeffectiveness analysis: methods for quantitative synthesis in medicine. New York, Oxford University Press.
  26. Qu JT, Wang M, He HL, Tang Y, Ye XJ (2012). The prognostic value of elevated vascular endothelial growth factor in patients with osteosarcoma: a meta-analysis and systemic review. J Cancer Res Clin Oncol, 138, 819-25. https://doi.org/10.1007/s00432-012-1149-7
  27. Salas S, Bartoli C, Deville JL, et al (2007). Ezrin and alpha-smooth muscle actin are immunohistochemical prognostic markers in conventional osteosarcomas. Virchows Arch, 451, 999-1007. https://doi.org/10.1007/s00428-007-0474-8
  28. Shi RL, Li JF, Qu Y, et al (2006). Expression of Ezrin in gastric carcinoma and its significance. Zhonghua Wei Chang Wai Ke Za Zhi, 9, 433-5.
  29. Stang A (2010). Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol, 25, 603-5. https://doi.org/10.1007/s10654-010-9491-z
  30. Sun CX, Robb VA,Gutmann DH (2002). Protein 4.1 tumor suppressors: getting a FERM grip on growth regulation. J Cell Sci, 115, 3991-4000. https://doi.org/10.1242/jcs.00094
  31. Vaheri A, Carpen O, Heiska L, et al (1997). The ezrin protein family: membrane-cytoskeleton interactions and disease associations. Curr Opin Cell Biol, 9, 659-66. https://doi.org/10.1016/S0955-0674(97)80119-6
  32. Wang HJ, Zhu JS, Zhang Q, Sun Q, Guo H (2009). High level of ezrin expression in colorectal cancer tissues is closely related to tumor malignancy. World J Gastroenterol, 15, 2016-9. https://doi.org/10.3748/wjg.15.2016
  33. Wang YF, Shen JN, Xie XB, Wang J, Huang G (2011). Expression change of ezrin as a prognostic factor in primary osteosarcoma. Med Oncol, 28, S636-43. https://doi.org/10.1007/s12032-010-9684-z
  34. Xu-dong S, Feng LIN, Ping C, et al (2008). Expression of Ezrin protein and its relationship with lung metastasis and survival time of osteosarcoma patients. TUMOR, 28, 4.
  35. Xu-Dong S, Zan S, Shui-er Z, et al (2009). Expression of Ezrin correlates with lung metastasis in Chinese patients with osteosarcoma. Clin Invest Med, 32, E180-8.
  36. You-yuan W, Wei-liang C, Zhao-hui Y, et al (2009). Effects of Ezrin gene on the proliferation and invasion activity of human salivary gland adenoid cystic carcinoma. Chin J Stomatol, 44, 5.
  37. Yu Y, Khan J, Khanna C, et al (2004). Expression profiling identifies the cytoskeletal organizer ezrin and the developmental homeoprotein Six-1 as key metastatic regulators. Nat Med, 10, 175-81. https://doi.org/10.1038/nm966

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