Thyroid cancer is the most prevalent malignancy of the endocrine system. It is comprised mainly by papillary thyroid cancer (PTC, 80-85%) and follicular thyroid cancer (FTC, 10-15%). PTC generally presents lymph-node metastasis (LNM), although both histological types have good prognosis. Nonetheless, the preoperative diagnosis of thyroid tumour malignancy, based on cytology of fine needle aspiration biopsies, results in up to 30% of indeterminate results, failing to distinguish between FTC and its benign counterpart follicular adenoma (FA).
Using iTRAQ protein labelling and mass spectrometry, we have performed a comprehensive proteomic study of the three most common tumours of the thyroid gland, analysing 9 FAs, 8 FTCs and 10 PTCs (LNM-positive and five with recurrence).
When compared with FA and FTC, PTC showed differential expression of key proteins associated with cell locomotion (e.g. E-cadherin, WAVE2, actin, members of the Arp2/3 complex). Functional analysis with IPA software showed enrichment of the biological functions ‘cellular growth and proliferation’ and ‘cellular movement’. In addition, two common molecular pathways significantly enriched were ‘actin cytoskeleton signalling’ and ‘remodelling of epithelial adherens junctions’ (probable disruption of cell contacts), which underlie cellular motility. Altogether, the results are in agreement with a favoured migratory activity and nodal invasion in PTC.
Our study revealed that the distinction between papillary and follicular tumours (FA+FTC) can be made with one single protein (e.g. galectin-3 or lipid phosphate phosphohydrolase 3). It also demonstrated the high protein level similarity between FA and FTC (only 38 differences). However, the combination of the 75 kDa extracellular protein TGF-b-induced protein ig-h3 (TGFBIp) with insulin-like growth factor-binding protein 5 (IGFBP5) achieved perfect separation between these two types of follicular tumours in this small cohort. Reduced expression of biglycan was observed in recurrent PTC samples. Our data supports further studies to investigate these proteins as ancillary diagnostic markers.