Biomarkers Correlating With the Development of Oral Squamous Cell Carcinoma From Leukoplakia

BACKGROUND: We assessed protein biomarkers expressed in oral leukoplakia (OL) that are associated with the risk of transformation into oral squamous cell carcinoma (OSCC). METHODS: Tissue sections of OL transforming into OSCC (leuko-ca), the corresponding OSCC and OL that did not progress to OSCC (leuko-nonca) were analyzed with global relative quantification to compare proteome profiles. Immunohistochemistry was performed to validate the expression of identified biomarkers. RESULTS: The top enriched biological pathways in OL transforming into OSCC within 5-26 months after diagnosis (short duration [SD]-leuko-ca) compared with leuko-nonca were pathways regulating remodeling of the extracellular matrix (ECM) and lipid and cholesterol metabolism/transport. Kininogen-1, apolipoprotein E (ApoE), collagen alpha-1 (XVIII) chain (COL18A1), sortilin, and perlecan were the most downregulated proteins, whereas EEF1D was the most upregulated in SD-leuko-ca compared with leuko-nonca. Immunohistochemistry confirmed the expression of kininogen-1, ApoE, perlecan, and EEF1D in OL and OSCC. In OSCC compared with leuko-ca, enriched biological pathways involved keratinocyte and epithelial differentiation and immune response regulation. CONCLUSION: We identified biomarkers in OL that were associated with the risk of malignant transformation. Our study gives further support for the importance of the immune system, ECM remodeling, and lipoproteins and cholesterol metabolism in the progression of OL to OSCC.