The prognostic value of ezrin expression in bone and soft tissue sarcomas: a meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

BI Hu ¹ , YI Zhigang ² , CHEN Bing ³ , ZHOU Kaishen ² , XU Donglin ¹ ,  PU Yanchuan ^1,2

1. Department of Orthopaedics, the People's Hospital of Wuwei, Wuwei, 733000, P.R.China;
2. Department of Orthopaedics, Second Hospital of Lanzhou University, Lanzhou, 730030, P.R.China;
3. Department of Hepatology, the People's Hospital of Wuwei, Wuwei, 733000, P.R.China;

Corresponding author：

PU Yanchuan, Email: pyc15@lzu.edu.cn

Keywords：

Bone and soft tissue sarcomas; Ezrin; Prognosis; Meta-analysis; Cohort study

DOI：

10.7507/1672-2531.201610014

Video：

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ObjectiveTo systematically review the predictive value of ezrin expression in bone and soft tissue sarcomas.MethodsDatabases including PubMed, EMbase, The Cochrane Library (Issue 2, 2016), CNKI, CBM, VIP, and WanFang Data were searched to collect cohort studies about the prognostic value of ezrin expression in bone and soft tissue sarcomas from inception to May 2016. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then meta-analysis was performed by using RevMan 5.3 software.ResultsFinally, a total of 17 cohort studies, involving 1 460 patients were included. The results of meta-analysis showed that: the overall survival (HR=1.90, 95%CI 1.70 to 2.13, P<0.000 01), event-free survival (HR=2.42, 95%CI 1.53 to 3.84, P=0.0002), metastasis-free survival (HR=2.09, 95%CI 1.10 to 3.97, P=0.02) in the bone and soft tissue sarcomas patients with ezrin high expression were lower than patients with lower expression. The same results were also observed in subgroup analysis according to histologica type and ethnicity in overall survival.ConclusionEzrin high expression may be used as a predictive maker for poor prognosis in bone and soft tissue sarcomas. For the quantity and quality limitation of the included studies, this conclusion still needs to be further proved by performing more high quality studies.

Citation： BIHu, YIZhigang, CHENBing, ZHOUKaishen, XUDonglin, PUYanchuan. The prognostic value of ezrin expression in bone and soft tissue sarcomas: a meta-analysis. Chinese Journal of Evidence-Based Medicine, 2017, 17(2): 180-187. doi: 10.7507/1672-2531.201610014 Copy

1.	Doyle LA. Sarcoma classification: an update based on the 2013 World Health Organization Classification of Tumors of Soft Tissue and Bone. Cancer, 2014, 120(12): 1763-1774.
2.	Hwang JS, Mehta AD, Yoon RS, et al. From amputation to limb salvage reconstruction: evolution and role of the endoprosthesis in musculoskeletal oncology. J Orthop Traumatol, 2014, 15(2): 81-86.
3.	Nakamura T, Matsumine A, Yamakado K, et al. Lung radiofrequency ablation in patients with pulmonary metastases from musculoskeletal sarcomas. Cancer, 2009, 115(16): 3774-3781.
4.	Zhang Y, Zhang L, Zhang G, et al. Osteosarcoma metastasis: prospective role of ezrin. Tumour Biol, 2014, 35(6): 5055-5059.
5.	Bruce B, Khanna G, Ren L, et al. Expression of the cytoskeleton linker protein ezrin in human cancers. Clin Exp Metastasis. 2007, 24(2): 69-78.
6.	Lugowska I, Mierzejewska E, Lenarcik M, et al. The clinical significance of changes in ezrin expression in osteosarcoma of children and young adults. Tumour Biol, 2016, 34(6): 5005-5009.
7.	Weng WH, Ahlén J, Aström K, et al. Prognostic impact of immunohistochemical expression of ezrin in highly malignant soft tissue sarcomas. Clin Cancer Res, 2005, 11(17): 6198-6204.
8.	Salas S, Bartoli C, Deville JL, et al. Ezrin and alpha-smooth muscle actin are immunohistochemical prognostic markers in conventional osteosarcomas. Virchows Arch, 2007, 451(6): 999-1007.
9.	Kim MS, Song WS, Cho WH, et al. Ezrin expression predicts survival in stage IIB osteosarcomas. Clin Orthop Relat Res, 2007, 459: 229-236.
10.	Kim MS, Cho WH, Song WS, et al. Prognostic significance of ezrin expression in pleomorphic malignant fibrous histiocytoma. Anticancer Res, 2007, 27(2): 1171-1178.
11.	沈旭东, 林峰, 陈平, 等. Ezrin蛋白表达及其与骨肉瘤肺转移生存期关系的研究. 肿瘤, 2008, 28(3): 260-262.
12.	Ferrari S, Zanella L, Alberghini M, et al. Prognostic significance of immunohistochemical expression of ezrin in non-metastatic high-grade osteosarcoma. Pediatr Blood Cancer, 2008, 50(4): 752-756.
13.	Kim C, Shin E, Hong S, et al. Clinical value of ezrin expression in primary osteosarcoma. Cancer Res Treat, 2009, 41(3): 138-144.
14.	杨建柱, 孙丽霞, 刘俊茹, 等. Ezrin蛋白在骨肉瘤中的表达及其意义. 肿瘤防治研究, 2008, 37(7): 818-821.
15.	Boldrini E, Peres SV, Morini S, et al. Immunoexpression of Ezrin and CD44 in patients with osteosarcoma. J Pediatr Hematol Oncol, 2010, 32(6): 213-217.
16.	Di Cristofano C, Leopizzi M, Miraglia A, et al. Phosphorylated ezrin is located in the nucleus of the osteosarcoma cell. Mod Pathol, 2010, 23(7): 1012-1020.
17.	Huang HY, Li CF, Fang FM, et al. Prognostic implication of ezrin overexpression in myxofibrosarcomas. Ann Surg Oncol, 2010, 17(12): 3212-3219.
18.	Wang YF, Shen JN, Xie XB, et al. Expression change of ezrin as a prognostic factor in primary osteosarcoma. Med Oncol, 2011, 28(1): 636-643.
19.	Carneiro A, Bendahl PO, Åkerman M, et al. Ezrin expression predicts local recurrence and development of metastases in soft tissue sarcomas. J Clin Pathol, 2011, 64(8): 689-694.
20.	闵大六, 沈赞, 林峰, 等. Runx2 和 Ezrin 基因在骨肉瘤组织中的表达及其临床意义. 中国癌症杂志, 2012, 22(9): 685-689.
21.	Le Guellec S, Moyal EC, Filleron T, et al. The β5/focal adhesion kinase/glycogen synthase kinase 3β integrin pathway in high-grade osteosarcoma: a protein expression profile predictive of response to neoadjuvant chemotherapy. Hum Pathol, 2013, 44(10): 2149-2158.
22.	Abdou AG, Kandil M, Asaad NY, et al. The Prognostic Role of Ezrin and HER2/neu Expression in Osteosarcoma. Appl Immunohistochem Mol Morphol, 2016, 24(5): 355-363.
23.	Palmerinii E, Benassi MS, Quattrini I, et al. Prognostic and predictive role of CXCR4, IGF-1R and Ezrin expression in localized synovial sarcoma: is chemotaxis important to tumor response? Orphanet J Rare Dis. 2015, 10: 2-8.
24.	Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol, 2010, 25(9): 603-605.
25.	Godwin A, Ponuwei. A glimpse of the ERM proteins. J Bio Sci, 2016, 23(1): 35-40.
26.	Brambilla D, Fais S. The Janus-faced role of ezrin in "linking" cells to either normal or metastatic phenotype. Int J Cancer, 2009, 125(10): 2239-2345.
27.	Safi AF, Nickenig HJ, Rothamel D, et al. Expression of ezrin in oral squamous cell carcinoma: Prognostic impact and clinicopathological correlations. J Craniomaxillofac Surg, 2015, 43(9): 1899-1905.
28.	Kong J, Li Y, Li, S, et al. High expression of ezrin predicts poor prognosis in uterine cervical cancer. BMC Cancer, 2013, 13(11): 520-527.
29.	Kang YK, Hong SW, Lee H, et al. Prognostic implications of ezrin expression in human hepatocellular carcinoma. Mol Carcinog, 2010, 49(9): 798-804.
30.	Mak H, Naba A, Varma S, et al. Ezrin phosphorylation on tyrosine 477 regulates invasion and metastasis of breast cancer cells. BMC Cancer, 2012, 82(12): 1407-1420.
31.	Wang X, Liu M, Zhao CY. Expression of ezrin and moesin related to invasion, metastasis and prognosis of laryngeal squamous cell carcinoma. Genet Mol Res, 2014, 13(3): 8002-8013.
32.	Lee HW, Kim EH, Oh MH. Clinicopathologic implication of ezrin expression in non-small cell lung cancer. Korean J Pathol, 2012, 46(5): 470-477.
33.	Li H, Min D, Zhao H, et al. The Prognostic Role of Ezrin Immunoexpression in Osteosarcoma: A Meta-Analysis of Published Data. PLoS One, 2013, 8(6): 64513.
34.	Lun DX, Hu YC, Xu ZW, et al. The prognostic value of elevated ezrin in patients with osteosarcoma. Tumour Biol, 2014, 35(2): 1263-1266.

1. Doyle LA. Sarcoma classification: an update based on the 2013 World Health Organization Classification of Tumors of Soft Tissue and Bone. Cancer, 2014, 120(12): 1763-1774.
2. Hwang JS, Mehta AD, Yoon RS, et al. From amputation to limb salvage reconstruction: evolution and role of the endoprosthesis in musculoskeletal oncology. J Orthop Traumatol, 2014, 15(2): 81-86.
3. Nakamura T, Matsumine A, Yamakado K, et al. Lung radiofrequency ablation in patients with pulmonary metastases from musculoskeletal sarcomas. Cancer, 2009, 115(16): 3774-3781.
4. Zhang Y, Zhang L, Zhang G, et al. Osteosarcoma metastasis: prospective role of ezrin. Tumour Biol, 2014, 35(6): 5055-5059.
5. Bruce B, Khanna G, Ren L, et al. Expression of the cytoskeleton linker protein ezrin in human cancers. Clin Exp Metastasis. 2007, 24(2): 69-78.
6. Lugowska I, Mierzejewska E, Lenarcik M, et al. The clinical significance of changes in ezrin expression in osteosarcoma of children and young adults. Tumour Biol, 2016, 34(6): 5005-5009.
7. Weng WH, Ahlén J, Aström K, et al. Prognostic impact of immunohistochemical expression of ezrin in highly malignant soft tissue sarcomas. Clin Cancer Res, 2005, 11(17): 6198-6204.
8. Salas S, Bartoli C, Deville JL, et al. Ezrin and alpha-smooth muscle actin are immunohistochemical prognostic markers in conventional osteosarcomas. Virchows Arch, 2007, 451(6): 999-1007.
9. Kim MS, Song WS, Cho WH, et al. Ezrin expression predicts survival in stage IIB osteosarcomas. Clin Orthop Relat Res, 2007, 459: 229-236.
10. Kim MS, Cho WH, Song WS, et al. Prognostic significance of ezrin expression in pleomorphic malignant fibrous histiocytoma. Anticancer Res, 2007, 27(2): 1171-1178.
11. 沈旭东, 林峰, 陈平, 等. Ezrin蛋白表达及其与骨肉瘤肺转移生存期关系的研究. 肿瘤, 2008, 28(3): 260-262.
12. Ferrari S, Zanella L, Alberghini M, et al. Prognostic significance of immunohistochemical expression of ezrin in non-metastatic high-grade osteosarcoma. Pediatr Blood Cancer, 2008, 50(4): 752-756.
13. Kim C, Shin E, Hong S, et al. Clinical value of ezrin expression in primary osteosarcoma. Cancer Res Treat, 2009, 41(3): 138-144.
14. 杨建柱, 孙丽霞, 刘俊茹, 等. Ezrin蛋白在骨肉瘤中的表达及其意义. 肿瘤防治研究, 2008, 37(7): 818-821.
15. Boldrini E, Peres SV, Morini S, et al. Immunoexpression of Ezrin and CD44 in patients with osteosarcoma. J Pediatr Hematol Oncol, 2010, 32(6): 213-217.
16. Di Cristofano C, Leopizzi M, Miraglia A, et al. Phosphorylated ezrin is located in the nucleus of the osteosarcoma cell. Mod Pathol, 2010, 23(7): 1012-1020.
17. Huang HY, Li CF, Fang FM, et al. Prognostic implication of ezrin overexpression in myxofibrosarcomas. Ann Surg Oncol, 2010, 17(12): 3212-3219.
18. Wang YF, Shen JN, Xie XB, et al. Expression change of ezrin as a prognostic factor in primary osteosarcoma. Med Oncol, 2011, 28(1): 636-643.
19. Carneiro A, Bendahl PO, Åkerman M, et al. Ezrin expression predicts local recurrence and development of metastases in soft tissue sarcomas. J Clin Pathol, 2011, 64(8): 689-694.
20. 闵大六, 沈赞, 林峰, 等. Runx2 和 Ezrin 基因在骨肉瘤组织中的表达及其临床意义. 中国癌症杂志, 2012, 22(9): 685-689.
21. Le Guellec S, Moyal EC, Filleron T, et al. The β5/focal adhesion kinase/glycogen synthase kinase 3β integrin pathway in high-grade osteosarcoma: a protein expression profile predictive of response to neoadjuvant chemotherapy. Hum Pathol, 2013, 44(10): 2149-2158.
22. Abdou AG, Kandil M, Asaad NY, et al. The Prognostic Role of Ezrin and HER2/neu Expression in Osteosarcoma. Appl Immunohistochem Mol Morphol, 2016, 24(5): 355-363.
23. Palmerinii E, Benassi MS, Quattrini I, et al. Prognostic and predictive role of CXCR4, IGF-1R and Ezrin expression in localized synovial sarcoma: is chemotaxis important to tumor response? Orphanet J Rare Dis. 2015, 10: 2-8.
24. Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol, 2010, 25(9): 603-605.
25. Godwin A, Ponuwei. A glimpse of the ERM proteins. J Bio Sci, 2016, 23(1): 35-40.
26. Brambilla D, Fais S. The Janus-faced role of ezrin in "linking" cells to either normal or metastatic phenotype. Int J Cancer, 2009, 125(10): 2239-2345.
27. Safi AF, Nickenig HJ, Rothamel D, et al. Expression of ezrin in oral squamous cell carcinoma: Prognostic impact and clinicopathological correlations. J Craniomaxillofac Surg, 2015, 43(9): 1899-1905.
28. Kong J, Li Y, Li, S, et al. High expression of ezrin predicts poor prognosis in uterine cervical cancer. BMC Cancer, 2013, 13(11): 520-527.
29. Kang YK, Hong SW, Lee H, et al. Prognostic implications of ezrin expression in human hepatocellular carcinoma. Mol Carcinog, 2010, 49(9): 798-804.
30. Mak H, Naba A, Varma S, et al. Ezrin phosphorylation on tyrosine 477 regulates invasion and metastasis of breast cancer cells. BMC Cancer, 2012, 82(12): 1407-1420.
31. Wang X, Liu M, Zhao CY. Expression of ezrin and moesin related to invasion, metastasis and prognosis of laryngeal squamous cell carcinoma. Genet Mol Res, 2014, 13(3): 8002-8013.
32. Lee HW, Kim EH, Oh MH. Clinicopathologic implication of ezrin expression in non-small cell lung cancer. Korean J Pathol, 2012, 46(5): 470-477.
33. Li H, Min D, Zhao H, et al. The Prognostic Role of Ezrin Immunoexpression in Osteosarcoma: A Meta-Analysis of Published Data. PLoS One, 2013, 8(6): 64513.
34. Lun DX, Hu YC, Xu ZW, et al. The prognostic value of elevated ezrin in patients with osteosarcoma. Tumour Biol, 2014, 35(2): 1263-1266.

Chinese Journal of Evidence-Based Medicine

The prognostic value of ezrin expression in bone and soft tissue sarcomas: a meta-analysis

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