Epithelial-to-Mesenchymal Transition and Neoangiogenesis in Laryngeal Squamous Cell Carcinoma

Abstract

The mechanism of epithelial–mesenchymal transition (EMT) is fundamental for carcinogenesis, tumor progression, cancer cell invasion, metastasis, recurrence, and therapy resistance, comprising important events, such as cellular junction degradation, downregulation of epithelial phenotype markers, overexpression of mesenchymal markers, and increase in cellular motility. The same factors that drive epithelial cells toward a mesenchymal phenotype may also drive endothelial cells toward a proangiogenic phenotype. The aim of this exploratory study was to investigate a potential interplay between EMT and angiogenesis (quantified through CD105 expression) in laryngeal carcinoma (LSCC). CD105-assessed microvessel density (MVD) and EMT markers (E-cadherin, N-cadherin, Snail, Slug, Zeb1, and Zeb2) were assessed on 37 consecutive LSCC cases. The univariate Cox regression model identified pN+ status (p = 0.0343) and Slug expression (p = 0.0268) as predictive of disease-free survival (DFS). A trend toward significance emerged for CD105-assessed MVD (p = 0.0869) and N-cadherin expression (p = 0.0911). In the multivariate Cox model, pN-status, Slug, and N-cadherin expressions retained their significant values in predicting DFS (p = 0.0346, p = 0.0430, and p = 0.0214, respectively). Our data support the hypothesis of a mutual concurrence of EMT and angiogenesis in driving LSCC cells toward an aggressive phenotype. To better characterize the predictive performance of prognostic models based on EMT and angiogenesis, further large-scale prospective studies are required.

Tumor-Stroma Ratio and Programmed Cell Death Ligand 1 Expression in Preoperative Biopsy and Matched Laryngeal Carcinoma Surgical Specimen

“…This is consistent with recent studies on colon cancer [ 23 , 24 ] and LSCC [ 10 ] and reflects the recently accepted view of both variables being markers of epithelial–mesenchymal transition (EMT). As is well-known, EMT is fundamental for carcinogenesis and shows prognostic implications also in LSCCs [ 25 ]. A mesenchymal (stromal) phenotype has been associated with an invasive front of the tumor where cancer cells (tumor budding) interface with stromal cells [ 26 ].…”

High CBX8 Expression Leads to Poor Prognosis in Laryngeal Squamous Cell Carcinoma by Inducing EMT by Activating the Wnt/β-Catenin Signaling Pathway

“…EMT transformation in LSCC has been reported. For example, Sun et al ( 39 ) found that DHA could inhibit EMT induced by IL-6 in LSCC cells through the miR-130B-3p/STAT3/β-catenin pathway, and the interaction between EMT and angiogenesis can improve the invasivity of LSCC ( 40 ). We concluded that the expression of E-cadherin increased after CBX8 knockdown, while the expression of N-cadherin and Snail1 decreased, suggesting that CBX8 may participate in the EMT process in LSCC.…”

Salt‐like transcription factor 4 promotes laryngeal cancer progression through transcriptional activation of ubiquitin‐specific protease 21 to stabilize Yin Yang 1

“…Laryngeal cancer is a common malignant cancer originating from the larynx 23 . The mechanisms of EMT underlie carcinogenesis, cancer progression, invasion, metastasis, recurrence, and therapy resistance 24 . However, EMT molecular mechanism in LC has not been thoroughly explored.…”

“…23 The mechanisms of EMT underlie carcinogenesis, cancer progression, invasion, metastasis, recurrence, and therapy resistance. 24 However, EMT molecular mechanism in LC has not been thoroughly explored. At present, we explored the action of SALL4/USP21/YY1 in LC.…”