High N-Cadherin Protein Expression in Ovarian Cancer Predicts Poor Survival and Triggers Cell Invasion

Abstract

Ovarian cancer (OC) is among the most lethal cancer among all gynaecological malignancies. Since most OC patients are diagnosed only at advanced stages mainly because of their imperceptible/nonspecific symptoms, survival rates are low. Therefore, more molecular biomarkers are needed to achieve more effective molecular stratification for better prognostic and theranostic outcomes. The cadherin family, particularly N-cadherin (N-CAD; also known as CDH2), is critical for cell-cell adhesion and epithelial- mesenchymal transition (EMT) of cancer. N-CAD protein has also been shown to be overexpressed in many advanced carcinomas. The aim of this study was to investigate the expression patterns of N-CAD protein, determine their correlations with the clinicopathological features of OC patients, and evaluate its prognostic value and involvement in EMT and metastasis. Protein expression of N-CAD was studied in 117 formalin-fixed and paraffin-embedded (FFPE) blocks from patients diagnosed with OC using Tissue Microarray and immunohistochemistry techniques. The N-CAD protein was overexpressed in 58% of our OC cohort. Furthermore, its cytoplasmic overexpression was significantly correlated with tumor grade (p= 0.05), tumor subtype (p= 0.05), tumor necrosis (p= 0.01), and age at menarche (p= 0.002). Interestingly, Kaplan-Meier analysis showed a significant correlation of disease-free survival (DFS) with OC patients with cytoplasmic N-CAD overexpression (p< 0.03, log rank). Patients with high N-CAD expression have approximately twice the recurrence rate at 5-year follow-up. The results of this study demonstrate a poor prognostic role of N-CAD overexpression in OC, which is reflected in higher recurrence and death rates of OC and its molecular contribution to EMT and distant metastasis. Therefore, OC patients with overexpressed N-CAD need to be monitored more frequently and closely. Further studies with larger patient cohorts are needed to validate these findings, demystify the role of N-CAD in OC pathophysiology, and further investigate its role as a potential therapeutic target.

Detection of Mesothelial-to-Mesenchymal Transition-Derived Carcinoma-Associated Fibroblasts in Primary Ovarian Carcinomas

“…In fact, the mesothelium of continuity and the OSE share the basal expression of several markers, including among others E-cadherin, N-cadherine, cytokeratins, mesothelin, WT1, CA125/MUC16 and neuropilin-1 [5,39]. Interenstingly, among these mesothelial/epithelial ovarian surface markers, CA125, N-cadherin, cytokeratins, mesothelin and neuropilin-1 are also frequently detected in epithelial OC cells [40][41][42][43][44]. In fact, ovarian stem cells existing within the OSE may be responsible for epithelial ovarian tumorogenesis by an EMT mechanism [1,6].…”

Dynamin 1-mediated endocytic recycling of glycosylated N-cadherin sustains the plastic mesenchymal state to promote ovarian cancer metastasis

“…Various clinical data have implicated the close association between EMT and ovarian cancer progression and therapy resistance. Whereas high expression of E-cadherin is associated with better patient survival and reduced invasiveness, elevated levels of N-cadherin have been correlated with worse clinical outcomes (Veatch et al, 1994;Klymenko et al, 2017;Assidi, 2022).…”

PEPITEM Treatment Ameliorates EAE in Mice by Reducing CNS Inflammation, Leukocyte Infiltration, Demyelination, and Proinflammatory Cytokine Production

“…Interestingly, cancer research suggests that N-cadherin in cancerous cells, in addition to other molecules, enables tumor invasion [30]. The mortality rate of patients with ovarian cancer is increased when N-cadherin is overexpressed [31].…”