Secretome-Based Identification and Characterization of Potential Biomarkers in Thyroid Cancer

Joseph and Mildred Sonshine Family Centre for Head and Neck Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada.
Journal of Proteome Research (Impact Factor: 5). 11/2010; 9(11):5757-69. DOI: 10.1021/pr100529t
Source: PubMed

ABSTRACT In search of thyroid cancer biomarkers, proteins secreted by thyroid cancer cell lines, papillary-derived TPC-1 and anaplastic-derived CAL62, were analyzed using liquid chromatography-tandem mass spectrometry. Of 46 high-confidence identifications, 6 proteins were considered for verification in thyroid cancer patients' tissue and blood. The localization of two proteins, nucleolin and prothymosin-α (PTMA), was confirmed in TPC-1 and CAL62 cells by confocal microscopy and immunohistochemically in xenografts of TPC-1 cells in NOD/SCID/γ mice and human thyroid cancers (48 tissues). Increased nuclear and cytoplasmic expression of PTMA was observed in anaplastic compared to papillary and poorly differentiated carcinomas. Nuclear expression of nucleolin was observed in all subtypes of thyroid carcinomas, along with faint cytoplasmic expression in anaplastic cancers. Importantly, PTMA, nucleolin, clusterin, cysteine-rich angiogenic inducer 61, enolase 1, and biotinidase were detected in thyroid cancer patients' sera, warranting future analysis to confirm their potential as blood-based thyroid cancer markers. In conclusion, we demonstrated the potential of secretome analysis of thyroid cancer cell lines to identify novel proteins that can be independently verified in cell lines, xenografts, tumor tissues, and blood samples of thyroid cancer patients. These observations support their potential utility as minimally invasive biomarkers for thyroid carcinomas and their application in management of these diseases upon future validation.

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    • "Previously, our study of the secretomes of two TC cell lines, a papillary-derived cell line (TPC-1) and an anaplasticderived cell line (CAL62), demonstrated that secretome proteins are detectable in sera and tissues of TC patients [24]. We identified 46 high-confidence protein IDs in the previous study and confirmed some of the identified proteins in TC patients' samples to assess their clinical significance. "
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    Proteomics 03/2013; 13(5). DOI:10.1002/pmic.201200356 · 3.97 Impact Factor
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    • "The criteria of selecting candidates for verification were (i) identification in our earlier iTRAQ studies; (ii) biological relevance; and (iii) prognostic relevance established in tissues in our earlier studies [20] [21] [52] "
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