Biomarkers Correlating with the Development of Oral Squamous Cell Carcinoma from Leukoplakia

We here assessed protein biomarkers expressed in oral leukoplakia (OL) associated with the risk of transformation to oral squamous cell carcinoma (OSCC). Tissue specimen sections of OL transforming into OSCC (leuko-ca), the corresponding OSCC and OL not developing to OSCC (leuko-nonca) were analyzed with proteomics using nano-liquid chromatography-mass spectrometry, and immunohistochemistry was performed on identified biomarkers. The top enriched biological pathways in OL turning to OSCC within 5–26 months from diagnosis (short duration (SD)-leuko-ca) vs. leuko-nonca were Cytoplasmic translation, Gene expression and Ribosomal large subunit biogenesis. Kininogen-1, apolipoprotein E (apoE), collagen alpha-1(XVIII) chain, sortilin and perlecan were top down-regulated candidate biomarkers, while EEF1D was the top up-regulated biomarker in SD-leuko-ca compared with leuko-nonca. The expressions in OL and OSCC of kininogen-1, apoE, perlecan and EEF1D were confirmed by immunohistochemistry. The top enriched biological pathways in OSCC compared with leuko-ca were Skin development, Antigen processing and presentation of endogenous peptide antigen, Epidermis development, Keratinocyte differentiation, Antigen processing and presentation of peptide antigen via MHC class Ib, Antigen processing and presentation of peptide antigen and Immune response. In conclusion, we have identified biomarkers in OL correlating with the risk of malignant transformation where the immune system seems to play an important role.