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Secretome proteins as candidate biomarkers for aggressive thyroid carcinomas

Authors

  • Seham Chaker,

    1. Alex and Simona Shnaider Laboratory in Molecular Oncology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada
    2. Institute of Medical Science, University of Toronto, Toronto, ON, Canada
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  • Lawrence Kashat,

    1. Alex and Simona Shnaider Laboratory in Molecular Oncology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada
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  • Sebastien Voisin,

    1. Department of Chemistry and Centre for Research in Mass Spectrometry, York University, Toronto, ON, Canada
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  • Jatinder Kaur,

    1. Alex and Simona Shnaider Laboratory in Molecular Oncology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada
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  • Ipshita Kak,

    1. Alex and Simona Shnaider Laboratory in Molecular Oncology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada
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  • Christina MacMillan,

    1. Department of Pathology & Laboratory Medicine, Mount Sinai Hospital, Toronto, ON, Canada
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  • Hilmi Ozcelik,

    1. Samuel Lunenfeld Research Institute, Mount Sinai Hospital L6–303, Toronto, ON, Canada
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  • K. W. Michael Siu,

    1. Department of Chemistry and Centre for Research in Mass Spectrometry, York University, Toronto, ON, Canada
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  • Ranju Ralhan,

    Corresponding author
    1. Institute of Medical Science, University of Toronto, Toronto, ON, Canada
    2. Department of Pathology & Laboratory Medicine, Mount Sinai Hospital, Toronto, ON, Canada
    3. Joseph and Mildred Sonshine Family Centre for Head and Neck Diseases, Department of Otolaryngology-Head and Neck Surgery Program, Mount Sinai Hospital, Toronto, ON, Canada
    4. Department of Otolaryngology-Head and Neck Surgery, University of Toronto, Toronto, ON, Canada
    • Alex and Simona Shnaider Laboratory in Molecular Oncology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada
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  • Paul G. Walfish

    1. Alex and Simona Shnaider Laboratory in Molecular Oncology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada
    2. Institute of Medical Science, University of Toronto, Toronto, ON, Canada
    3. Department of Pathology & Laboratory Medicine, Mount Sinai Hospital, Toronto, ON, Canada
    4. Joseph and Mildred Sonshine Family Centre for Head and Neck Diseases, Department of Otolaryngology-Head and Neck Surgery Program, Mount Sinai Hospital, Toronto, ON, Canada
    5. Department of Medicine, Endocrine Division, Mount Sinai Hospital and University of Toronto Medical School, Toronto, ON, Canada
    6. Department of Otolaryngology-Head and Neck Surgery, University of Toronto, Toronto, ON, Canada
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  • Colour Online: See the article online to view Figs. 2 and 3 in colour.

Correspondence: Professor Ranju Ralhan, Joseph and Mildred Sonshine Family Centre for Head and Neck Diseases, Department of Otolaryngology-Head and Neck Surgery Program, Mount Sinai Hospital, Joseph & Wolf Lebovic Health Complex, 600 University Avenue, Room 4–413, Toronto, Ontario, Canada M5G 1X5

E-mail: rralhan@mtsinai.on.ca

Fax: +416-586-8861

Abstract

Using proteomics in tandem with bioinformatics, the secretomes of nonaggressive and aggressive thyroid carcinoma (TC) cell lines were analyzed to detect potential biomarkers for tumor aggressiveness. A panel of nine proteins, activated leukocyte cell adhesion molecule (ALCAM/CD166), tyrosine-protein kinase receptor (AXL), amyloid beta A4 protein, amyloid-like protein 2, heterogeneous nuclear ribonucleoprotein K, phosphoglycerate kinase 1, pyruvate kinase isozyme M2, phosphatase 2A inhibitor (SET), and protein kinase C inhibitor protein 1 (14–3-3 zeta) was chosen to confirm their expression in TC patients’ sera and tissues. Increased presurgical circulating levels of ALCAM were associated with aggressive tumors (p = 0.04) and presence of lymph node metastasis (p = 0.018). Increased serum AXL levels were associated with extrathyroidal extension (p = 0.027). Furthermore, differential expression of amyloid beta A4 protein, AXL, heterogeneous nuclear ribonucleoprotein K, phosphoglycerate kinase 1, pyruvate kinase muscle isozyme M2, and SET was observed in TC tissues compared to benign nodules. Decreased nuclear expression of AXL can detect malignancy with 90% specificity and 100% sensitivity (AUC = 0.995, p < 0.001). In conclusion, some of these proteins show potential for future development as serum and/or tissue-based biomarkers for TC and warrant further investigation in a large cohort of patients.

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