Proteomics profiling of keratocystic odontogenic tumours reveals AIDA as novel biomarker candidate.

Abstract

Keratocystic odontogenic tumour (KCOT) is a benign, yet aggressive odontogenic tumour. Herein, proteome analysis of KCOT lesions in comparison with control patient-matched tissue unaffected by the disease and with inflammatory odontogenic cysts, namely radicular cysts is presented. For the proteomics profiling, two complementary proteomics techniques MALDI-MS/MS and LC-ESI-MS/MS were employed. Potential candidate biomarkers were validated by immunohistochemistry. More than 43 proteins were found to be differentially expressed or up-regulated in KCOT lesions in comparison with patient-matched unaffected oral mucosa. These proteins bear important biological functions and are involved in cell proliferation, cytoskeletal re-organization, transcription, cellular motility and apoptosis. In particular, a number of differentially expressed proteins participate in autocrine regulation and signalization within JNK and p38 MAPK signalling pathways. Immunohistochemical validation of chosen putative biomarkers revealed axin interaction partner and dorsalization-antagonist (AIDA), known as a protein that blocks activation of JNK signalling pathway, as a differential biomarker for KCOT lesions on an independent cohort of KCOT tissue samples in comparison with most prevalent intra-oseal lesions inflammatory odontogenic cysts.