The Expression of YKL-40 Protein in Oral Potentially Malignant Disorders (OPMD) and Oral Squamous Cell Carcinoma (OSCC)

Nur Fatinazwa Mohd Faizal¹, Karen-Ng Lee Peng², Zuraiza Mohamad Zaini^1,2,*

Abstract

Introduction: Oral squamous carcinoma cell (OSCC) is the most common type of oral cancer, which results in significant morbidity and mortality. In OSCC, the progression from normal mucosa to different grades of dysplasia and to invasive carcinoma is characterized by an increased formation of angiogenesis. There is much evidence that indicated YKL-40, a secreted glycoprotein, was highly elevated in cancers and associated with tumour angiogenesis. Being a potent angiogenic factor capable of stimulating development and vascularization of tumour during carcinogenesis, the role of YKL-40 in oral dysplasia and its progression remains unknown. Hence, this study aims to determine the expression of YKL-40 in OSCC and its potential role in the oral carcinogenesis. Methods: Secreted YKL-40 protein levels were screened by enzyme-linked immunosorbent assays (ELISA) in serum samples from 16 healthy donors, 14 oral precancer and 22 OSCC patients as well as conditioned media collected from oral epithelial dysplasia (OED) and OSCC cell lines. In addition, we employed immunohistochemical (IHC) detection in 75 oral tissue samples consisting of 20 normal oral mucosa (NOM), 35 OED and 20 OSCC cases. To determine the effect of YKL-40 on vascular endothelial angiogenesis, migration assay and tube formation assay of human umbilical vein endothelial cell (HUVEC) was performed. Results: YKL-40 protein expression in serum was the highest in OSCC followed by oral dysplasia and normal samples. Similar trend was seen in cell lines whereby OSCC exhibited higher YKL-40 expression as compared to dysplasia cell lines. IHC results showed that YKL-40 was highly expressed across the epithelium in OSCC, and OED compared to NOM tissue. Additional of exogenous recombinant YKL-40 prompted HUVEC migration and tube formation compared to control. Notably, YKL-40 also enhanced migration of HUVEC induced by conditioned medium of OSCC cells. Conclusion: These findings provide novel insights into angiogenic activities of YKL-40 in oral cancer development.

Keywords: Oral squamous carcinoma cell, Oral epithelial dysplasia, Angiogenesis

References