Clinical Significance of Claudin Expression in Oral Squamous Cell Carcinoma

Abstract

A change in claudin expression has been demonstrated in various tumors. The present study specifically compares claudin expression in oral squamous cell carcinoma (OSCC) with healthy oral epithelium from the same individual and analyzes the association between claudin expression and the clinically relevant course parameters. Our study includes tissue samples and clinically relevant follow-up data from 60 patients with primary and untreated OSCC. The oral mucosa was analyzed via Western blot for the expression of claudin-1, -2, -3, -4, -5, and -7. Importantly, the tumor and healthy tissues were obtained pairwise from patients, allowing for intraindividual comparisons. Both the healthy and tumor epithelium from the oral cavity did not express the claudin-3 protein. The intraindividual comparison revealed that, in OSCC, claudin-2 expression was higher, and the expression of claudin-4, -5, and -7 was lower than in healthy epithelium. An association was found between increased claudin-2 expression and shorter relapse-free survival. In addition, the reduced expression of claudin-4 had a negative impact on relapse-free survival. Furthermore, associations between the reduced expression of claudin-7 and the stage of a tumor, or the presence of lymph node metastases, were found. Thus, the expression level of claudin-2, -4, and -7 appears to be predictive of the diagnosis and prognosis of OSCC.

Aberrant Expression of Claudins in Head and Neck Carcinomas and Their Prognostic and Therapeutic Value: A Narrative Review

“…The same study also found no linkage between claudin-1 expression and patient health outcome. Zejc et al reported similar results, where claudin-1 expression was not correlated to tumor stage, expansion, histological differentiation, recurrence-free survival, and several other clinicopathological parameters [40]. On the other hand, reports have found significant positive associations between pathological grade, perineural and vascular invasion, nodal metastasis, and advanced tumor staging [42].…”

“…Although the exact role of claudins is not very well understood in cancer progression, claudin-1 is a frequently studied protein in the literature. In oral squamous cell carcinoma (OSCC), claudin-1 expression levels ranged from high to no change [40]. Over-expression of claudin-1 correlates with higher histological grades, specifically when the protein is positioned intracellularly, compared to when it is membranous or cytoplasmically expressed [37].…”

“…In OSCC tissue, claudins-4, -5 and -7 are expressed significantly lower than normal tissue [39,40]. Specifically, downregulation of claudin-4 has been reported to predict reduced recurrence-free survival [40].…”

The Expression of the Claudin Family of Proteins in Colorectal Cancer

“…Claudin-2 (CLDN2), first described by Furuse et al in 1998, has been found to be highly expressed in the liver and kidney [ 12 , 65 ]. In cancerous tissues, it has been shown to be downregulated in breast carcinoma and upregulated in oral squamous cell cancer compared to normal tissues [ 16 , 19 ].…”

“…Despite this apparent advantage of downregulating tight junction proteins, there are a tremendous number of reports on the upregulation of claudins in cancer [ 10 ]. This includes claudin-2 in oral squamous cell cancer, claudin-3 in ovarian and laryngeal cancers, and claudin-10 in papillary thyroid cancer [ 19 , 20 , 21 , 22 ]. While previous review articles have highlighted numerous claudin proteins’ dysregulation in cancer, there has yet to be a comprehensive report on the expression profiles of the claudin family of proteins in CRC and the ability to use levels of claudin expression for prognostication.…”