The Role of E-Cadherin as a Prognostic Biomarker in Head and Neck Squamous Carcinoma: A Systematic Review and Meta-Analysis
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In this study, we systematically investigated and analyzed articles focusing on the prognostic value of E-cadherin (E-cad) in human head and neck squamous cell carcinoma (HNSCC).
Searching through the different databases, the studies examining the associations between E-cad and HNSCC prognosis were identified. Outcomes such as disease-specific survival and overall survival were considered acceptable. Hazard ratio (HR) with 95% confidence interval (CI) was used to demonstrate prognostic value.
A total of 40 studies were systematically analyzed, and finally, 1939 subjects were included in our meta-analysis. Our findings showed that significant aberrant expression of E-cad was associated with poor survival. However, some studies showed increased expression of E-cad in metastatic lesions was associated with poor prognosis. Alteration in location of E-cad expression also showed significant association with cancer survival, i.e., increased cytoplasmic E-cad. We conducted a meta-analysis on the eligible articles using a random effect model because of moderate heterogeneity. Strong association between aberrant expression of E-cad and poor survival was demonstrated (pooled HR = 2.28; 95% CI 1.78–2.91).
Aberrant expression of E-cad may be a promising prognostic signature for HNSCC, especially when it is used with other prognostic markers.
Compliance with Ethical Standards
Non funding to declare.
Conflict of interest
None declared by all authors: Javad Yazdani, Mohhamad Ali Ghavimi, Elahe Jabbari Hagh and Farzin Ahmadpour.
- 4.Zhao Z, Ge J, Sun Y, Tian L, Lu J, Liu M, et al. Is E-cadherin immunoexpression a prognostic factor for head and neck squamous cell carcinoma (HNSCC)? A systematic review and meta-analysis. Oral Oncol. 2012;48(9):761–7. https://doi.org/10.1016/j.oraloncology.2012.02.024.CrossRefPubMedGoogle Scholar
- 8.(US), N. C. f. B. I. (2005). PubMed Help [Internet]. http://www.ncbi.nlm.nih.gov/books/NBK3827/#pubmedhelp.Appendices.
- 12.Muller S, Su L, Tighiouart M, Saba N, Zhang H, Shin DM, et al. Distinctive E-cadherin and epidermal growth factor receptor expression in metastatic and nonmetastatic head and neck squamous cell carcinoma: predictive and prognostic correlation. Cancer. 2008;113(1):97–107. https://doi.org/10.1002/cncr.23557.CrossRefPubMedGoogle Scholar
- 15.Pyo SW, Hashimoto M, Kim YS, Kim CH, Lee SH, Johnson KR, et al. Expression of E-cadherin, P-cadherin and N-cadherin in oral squamous cell carcinoma: correlation with the clinicopathologic features and patient outcome. J Craniomaxillofac Surg. 2007;35(1):1–9. https://doi.org/10.1016/j.jcms.2006.11.004.CrossRefPubMedGoogle Scholar
- 17.Diniz-Freitas M, Garcia-Caballero T, Antunez-Lopez J, Gandara-Rey JM, Garcia-Garcia A. Reduced E-cadherin expression is an indicator of unfavourable prognosis in oral squamous cell carcinoma. Oral Oncol. 2006;42(2):190–200. https://doi.org/10.1016/j.oraloncology.2005.07.010.CrossRefPubMedGoogle Scholar
- 19.Ukpo OC, Thorstad WL, Zhang Q, Lewis JS Jr. Lack of association of cadherin expression and histopathologic type, metastasis, or patient outcome in oropharyngeal squamous cell carcinoma: a tissue microarray study. Head Neck Pathol. 2012;6(1):38–47. https://doi.org/10.1007/s12105-011-0306-7.CrossRefPubMedGoogle Scholar
- 21.Liu LK, Jiang XY, Zhou XX, Wang DM, Song XL, Jiang HB. Upregulation of vimentin and aberrant expression of E-cadherin/beta-catenin complex in oral squamous cell carcinomas: correlation with the clinicopathological features and patient outcome. Mod Pathol. 2010;23(2):213–24. https://doi.org/10.1038/modpathol.2009.160.CrossRefPubMedGoogle Scholar
- 28.Ueda G, Sunakawa H, Nakamori K, Shinya T, Tsuhako W, Tamura Y, et al. Aberrant expression of beta- and gamma-catenin is an independent prognostic marker in oral squamous cell carcinoma. Int J Oral Maxillofac Surg. 2006;35(4):356–61. https://doi.org/10.1016/j.ijom.2005.07.023.CrossRefPubMedGoogle Scholar
- 33.da Silva SD, Morand GB, Alobaid FA, Hier MP, Mlynarek AM, Alaoui-Jamali MA, et al. Epithelial-mesenchymal transition (EMT) markers have prognostic impact in multiple primary oral squamous cell carcinoma. Clin Exp Metastasis. 2015;32(1):55–63. https://doi.org/10.1007/s10585-014-9690-1.CrossRefPubMedGoogle Scholar
- 34.Huber GF, Zullig L, Soltermann A, Roessle M, Graf N, Haerle SK, et al. Down regulation of E-Cadherin (ECAD)—a predictor for occult metastatic disease in sentinel node biopsy of early squamous cell carcinomas of the oral cavity and oropharynx. BMC Cancer. 2011;11(217):211–8. https://doi.org/10.1186/1471-2407-11-217.CrossRefGoogle Scholar
- 36.Kurtz KA, Hoffman HT, Zimmerman MB, Robinson RA. Decreased E-cadherin but not beta-catenin expression is associated with vascular invasion and decreased survival in head and neck squamous carcinomas. Otolaryngol Head Neck Surg. 2006;134(1):142–6. https://doi.org/10.1016/j.otohns.2005.08.026.CrossRefPubMedGoogle Scholar
- 37.Wang X, Zhang J, Fan M, Zhou Q, Deng H, Aisharif MJ, et al. The expression of E-cadherin at the invasive tumor front of oral squamous cell carcinoma: immunohistochemical and RT-PCR analysis with clinicopathological correlation. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2009;107(4):547–54. https://doi.org/10.1016/j.tripleo.2008.11.021.CrossRefPubMedGoogle Scholar
- 41.Zhao D, Tang XF, Yang K, Liu JY, Ma XR. Over-expression of integrin-linked kinase correlates with aberrant expression of Snail, E-cadherin and N-cadherin in oral squamous cell carcinoma: implications in tumor progression and metastasis. Clin Exp Metastasis. 2012;29(8):957–69. https://doi.org/10.1007/s10585-012-9485-1.CrossRefPubMedGoogle Scholar
- 46.Wang C, Huang H, Huang Z, Wang A, Chen X, Huang L, et al. Tumor budding correlates with poor prognosis and epithelial-mesenchymal transition in tongue squamous cell carcinoma. J Oral Pathol Med. 2011;40(7):545–51. https://doi.org/10.1111/j.1600-0714.2011.01041.x.CrossRefPubMedPubMedCentralGoogle Scholar
- 47.Rosado P, Lequerica-Fernandez P, Fernandez S, Allonca E, Villallain L, de Vicente JC. E-cadherin and beta-catenin expression in well-differentiated and moderately-differentiated oral squamous cell carcinoma: relations with clinical variables. Br J Oral Maxillofac Surg. 2013;51(2):149–56. https://doi.org/10.1016/j.bjoms.2012.03.018.CrossRefPubMedGoogle Scholar