Overexpression of E-Cadherin Is a Favorable Prognostic Biomarker in Oral Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis

Abstract

Oral squamous cell carcinoma (OSCC) is characterized by poor survival, mostly due to local invasion, loco-regional recurrence, and metastasis. Given that the weakening of cell-to-cell adhesion is a feature associated with the migration and invasion of cancer cells, different studies have explored the prognostic utility of cell adhesion molecules such as E-cadherin (E-cad). This study aims to summarize current evidence in a meta-analysis, focusing on the prognostic role of E-cad in OSCC. To find studies meeting inclusion criteria, Scopus, Web of Science, EMBASE, Medline, and OpenGrey databases were systematically assessed and screened. The selection process led to 25 studies, which were considered eligible for inclusion in the meta-analysis, representing a sample of 2553 patients. E-cad overexpression was strongly associated with longer overall survival (OS) with Hazard Ratio (HR) = 0.41 95% confidence interval (95% CI) (0.32-0.54); p < 0.001 and disease-free survival with HR 0.47 95% CI (0.37-0.61); p < 0.001. In terms of OS, patients with tongue cancer experienced better survivability when expressing E-cad with HR 0.28 95% CI (0.19-0.43); p < 0.001. Globally, our findings indicate the prognostic role of the immunohistochemical assessment of E-cad in OSCC and its expression might acquire a different role based on the oral cavity subsites.

Keywords: E-cadherin; epithelial-mesenchymal transition; meta-analysis; mouth neoplasm; prognostic; systematic review.

Figure 1

The descriptive diagram model of composition and interactions between proteins that are part of the cell union complex. (A) The Occlusion Junctions seal the spaces between epithelial cells, and it is of paramount importance in sealing the epithelial tissues to water molecules and ions, making the passive diffusion of ions impossible; here Occludins and Claudins act. (B) The Adherens Junctions connect the bundles of Actin Filaments of one cell with the bundles of another cell where the primary function is to promote adhesion between neighboring cells being crucial in tissue architecture; here Cadherins, α-Catenins, β-Catenins, p120-Catenin, and Vinculins acts. The regulation of the cell–cell adhesion complex is mediated by E-Cadherin and can favor the transformation of epithelial cells into mesenchymal cells after triggering EMT inducers in the various pathways involved; among those involved, the SNAIL protein helps to promote this process by blocking the E-Cadherin. (C) Desmosomes connect the Intermediate Filaments of one cell with those of the other cell, with the main aim of promoting intercellular adhesion, not interfering with other junctions; here Desmogleins, Desmocolins, Plakoglobin, Desmoplakin, and the Intermediate Filaments are involved. (D) The Gap Junctions allow the passage of water-soluble molecules from one cell to another; it is formed by six subunits of Connexins forming a hexagonal complex. (E) Hemidesmosomes anchor the cell’s Intermediate Filaments to the Extracellular Matrix—Cell/Matrix adhesion anchors the Actin Filaments of the cell to the Extracellular Matrix, connecting the Intermediate Filaments of the Cytoskeleton with the Extracellular Matrix; here α-Integrins and β-Integrins are involved.

Figure 2

PRISMA 2020 flow diagram.

Figure 3

(A) Forest plots of overall survival and (B) disease-free survival. Horizontal axis represents Hazard Ratios.