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Differential Expression of P53, CDKN2A, NOTCH1, and CASP8 in Oral Epithelial Dysplasia: An In Vitro Study to Explore
Md Omar Faruk1,2, Lee Peng Karen-Ng2, Wanninayake Mudiyanselage Tilakaratne1,2
1Department of Oral and Maxillofacial Clinical Sciences, Faculty of Dentistry, Universiti Malaya, Kuala Lumpur, Malaysia.
Objective:
This study aimed to better understand the expression of P53, CDKN2A, NOTCH1, and CASP8 proteins in progressive and nonprogressive oral epithelial dysplasia (OED) cell lines to predict malignant transformation.
Materials And Methods:
Normal oral keratinocytes (NHOK810), nonprogressive OED (D30-mild, D25-severe), progressive OED (D20-moderate, D19-severe), and oral squamous cell carcinoma (H357, BICR31, and ORL188) were co-cultured with irradiated 3T3 fibroblasts. Western blotting was used to assess the protein expression of p53, CDKN2A, NOTCH1, and CASP8 in these cell lines. Bootstrapping, one-way ANOVA, and subsequent post hoc analyses were performed for multiple comparisons.
Results:
CDKN2A and NOTCH1 had low expression in progressive OED (p = 0.0008 and 0.0012) respectively relative to nonprogressive OED, indicating a negative tendency. Conversely, p53 demonstrated significantly higher expression in progressive OED (p = 0.0112) compared to nonprogressive OED, reflecting a positive trend of expression throughout disease progression. There was a significant difference in CASP8 expression between nonprogressive and progressive cell lines (p = 0.039); however, no linear pattern was observed as the disease advanced.
Conclusion:
The current study illustrates that the high expression of p53, combined with low expression of CDKN2A and NOTCH1, may serve as helpful markers, providing a potential molecular complement to histopathology for predicting malignant transformation in OED.
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