Preliminary Study of the Cancer Stem Cells' Biomarker CD147 in Leukoplakia: Dysplasia and Squamous Cell Carcinoma of Oral Epithelial Origin

Abstract

Objectives Cancer stem cells (CSCs) are responsible for initiating the process of carcinogenesis de novo, as well as through the transformation of oral potential malignant disorders (OPMDs) to oral squamous cell carcinoma (OSCC). The aim of our study was to detect the expression of stemness-type CSC marker CD147 in oral leukoplakias (OLs), the most common OPMD, and OSCCs as well. Materials and methods This study focuses on the semiquantitative immunohistochemical pattern of the expression of the CSC protein biomarker CD147 in paraffin-embedded samples of 20 OSCCs of different grades of differentiation and 30 cases of OLs without or with different grades of dysplasia, compared to the normal oral epithelium in terms of cells' stain positivity. Statistical analysis was performed through Statistical Package for Social Sciences (SPSS) version 25.0 (IBM SPSS Statistics, Armonk, NY) with Pearson chi-square test, and the significance level was set at 0.05 (p=0.05). In addition, the study clarified the expression of the respective gene of CD147 through quantitative polymerase chain (qPCR), in paraffin-embedded samples of the two extreme graduations: OLs of mildly dysplastic or non-dysplastic cases (n=10 cases) and OSCCs of moderately/poorly differentiated cases (n=17). Statistical analysis was then performed through SPSS version 25.0 with an independent paired t-test, and the significance level was set at 0.05 (p=0.05). Results The gene CD147 was expressed in all cases, although no statistically significant correlations were established. Regarding its protein products, the characteristic membranous staining of CD147 was noticed in the majority of the samples, mostly in the basal and parabasal layers of the epithelium. CD147 was upregulated significantly in the moderately and severely dysplastic OLs than in the mildly dysplastic and non-dysplastic OLs (p=0.008). Also, CD147 was upregulated significantly in the mildly dysplastic and non-dysplastic OLs than in the normal oral epithelium (p=0.012). Discussion The characteristic expression of CD147 in OLs and OSCCs' lesions suggests the presence of stemlike cancer cells, illustrating an underlying effect on the early stages of oral dysplasia, in the OL stage. The clinical application of CD147 as prognostic factor requires the experimental evaluation in larger number of samples. Conclusion Stem cells play an important role in the process of carcinogenesis. A major goal in cancer research is the identification of specific biomarkers for the detection of cancer stem cells. CD147 is considered as an innovative stem cell marker. Our findings in oral mucosal potentially malignant disorders showed that CD147 is expressed more intensely in parallel with the progression of the grade of dysplasia in OL. On the other hand, in oral squamous cell carcinoma, CD147 expression remains stable regardless of the degree of differentiation.

Keywords: cancer stem cells; cd147; immunohistochemistry staining; oral cancers; oral leukoplakia; oscc; rt-qpcr.

Figure 1. CD147 expression in normal oral epithelium, OLs, and OSCCs.

OSCCs, oral squamous cell carcinomas; OLs, oral leukoplakias