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Serum Immunoproteomics Combined With Pathological Reassessment of Surgical Specimens Identifies TCP-1ζ Autoantibody as a Potential Biomarker in Thyroid Neoplasia.
Belousov, Pavel V; Bogolyubova, Apollinariya V; Kim, Yan S; Abrosimov, Alexander Y; Kopylov, Arthur T; Tvardovskiy, Andrey A; Lanshchakov, Kirill V; Sazykin, Alexei Y; Dvinskikh, Nina Y; Bobrovskaya, Yana I; Selivanova, Lilia S; Shilov, Evgeniy S; Schwartz, Anton M; Shebzukhov, Yuriy V; Severskaia, Natalya V; Vanushko, Vladimir E; Moshkovskii, Sergei A; Nedospasov, Sergei A; Kuprash, Dmitry V.
Affiliation
  • Belousov PV; Department of Immunology (P.V.B., A.V.B., Y.S.K., A.Y.S., Y.I.B., E.S.S., S.A.N., D.V.K.) Biological Faculty, Lomonosov Moscow State University, 119991 Moscow, Russia; Laboratory of Molecular Mechanisms of Immunity (A.V.B., S.A.N.), Engelhardt Institute of Molecular Biology, Russian Academy of Scien
  • Bogolyubova AV; Department of Immunology (P.V.B., A.V.B., Y.S.K., A.Y.S., Y.I.B., E.S.S., S.A.N., D.V.K.) Biological Faculty, Lomonosov Moscow State University, 119991 Moscow, Russia; Laboratory of Molecular Mechanisms of Immunity (A.V.B., S.A.N.), Engelhardt Institute of Molecular Biology, Russian Academy of Scien
  • Kim YS; Department of Immunology (P.V.B., A.V.B., Y.S.K., A.Y.S., Y.I.B., E.S.S., S.A.N., D.V.K.) Biological Faculty, Lomonosov Moscow State University, 119991 Moscow, Russia; Laboratory of Molecular Mechanisms of Immunity (A.V.B., S.A.N.), Engelhardt Institute of Molecular Biology, Russian Academy of Scien
  • Abrosimov AY; Department of Immunology (P.V.B., A.V.B., Y.S.K., A.Y.S., Y.I.B., E.S.S., S.A.N., D.V.K.) Biological Faculty, Lomonosov Moscow State University, 119991 Moscow, Russia; Laboratory of Molecular Mechanisms of Immunity (A.V.B., S.A.N.), Engelhardt Institute of Molecular Biology, Russian Academy of Scien
  • Kopylov AT; Department of Immunology (P.V.B., A.V.B., Y.S.K., A.Y.S., Y.I.B., E.S.S., S.A.N., D.V.K.) Biological Faculty, Lomonosov Moscow State University, 119991 Moscow, Russia; Laboratory of Molecular Mechanisms of Immunity (A.V.B., S.A.N.), Engelhardt Institute of Molecular Biology, Russian Academy of Scien
  • Tvardovskiy AA; Department of Immunology (P.V.B., A.V.B., Y.S.K., A.Y.S., Y.I.B., E.S.S., S.A.N., D.V.K.) Biological Faculty, Lomonosov Moscow State University, 119991 Moscow, Russia; Laboratory of Molecular Mechanisms of Immunity (A.V.B., S.A.N.), Engelhardt Institute of Molecular Biology, Russian Academy of Scien
  • Lanshchakov KV; Department of Immunology (P.V.B., A.V.B., Y.S.K., A.Y.S., Y.I.B., E.S.S., S.A.N., D.V.K.) Biological Faculty, Lomonosov Moscow State University, 119991 Moscow, Russia; Laboratory of Molecular Mechanisms of Immunity (A.V.B., S.A.N.), Engelhardt Institute of Molecular Biology, Russian Academy of Scien
  • Sazykin AY; Department of Immunology (P.V.B., A.V.B., Y.S.K., A.Y.S., Y.I.B., E.S.S., S.A.N., D.V.K.) Biological Faculty, Lomonosov Moscow State University, 119991 Moscow, Russia; Laboratory of Molecular Mechanisms of Immunity (A.V.B., S.A.N.), Engelhardt Institute of Molecular Biology, Russian Academy of Scien
  • Dvinskikh NY; Department of Immunology (P.V.B., A.V.B., Y.S.K., A.Y.S., Y.I.B., E.S.S., S.A.N., D.V.K.) Biological Faculty, Lomonosov Moscow State University, 119991 Moscow, Russia; Laboratory of Molecular Mechanisms of Immunity (A.V.B., S.A.N.), Engelhardt Institute of Molecular Biology, Russian Academy of Scien
  • Bobrovskaya YI; Department of Immunology (P.V.B., A.V.B., Y.S.K., A.Y.S., Y.I.B., E.S.S., S.A.N., D.V.K.) Biological Faculty, Lomonosov Moscow State University, 119991 Moscow, Russia; Laboratory of Molecular Mechanisms of Immunity (A.V.B., S.A.N.), Engelhardt Institute of Molecular Biology, Russian Academy of Scien
  • Selivanova LS; Department of Immunology (P.V.B., A.V.B., Y.S.K., A.Y.S., Y.I.B., E.S.S., S.A.N., D.V.K.) Biological Faculty, Lomonosov Moscow State University, 119991 Moscow, Russia; Laboratory of Molecular Mechanisms of Immunity (A.V.B., S.A.N.), Engelhardt Institute of Molecular Biology, Russian Academy of Scien
  • Shilov ES; Department of Immunology (P.V.B., A.V.B., Y.S.K., A.Y.S., Y.I.B., E.S.S., S.A.N., D.V.K.) Biological Faculty, Lomonosov Moscow State University, 119991 Moscow, Russia; Laboratory of Molecular Mechanisms of Immunity (A.V.B., S.A.N.), Engelhardt Institute of Molecular Biology, Russian Academy of Scien
  • Schwartz AM; Department of Immunology (P.V.B., A.V.B., Y.S.K., A.Y.S., Y.I.B., E.S.S., S.A.N., D.V.K.) Biological Faculty, Lomonosov Moscow State University, 119991 Moscow, Russia; Laboratory of Molecular Mechanisms of Immunity (A.V.B., S.A.N.), Engelhardt Institute of Molecular Biology, Russian Academy of Scien
  • Shebzukhov YV; Department of Immunology (P.V.B., A.V.B., Y.S.K., A.Y.S., Y.I.B., E.S.S., S.A.N., D.V.K.) Biological Faculty, Lomonosov Moscow State University, 119991 Moscow, Russia; Laboratory of Molecular Mechanisms of Immunity (A.V.B., S.A.N.), Engelhardt Institute of Molecular Biology, Russian Academy of Scien
  • Severskaia NV; Department of Immunology (P.V.B., A.V.B., Y.S.K., A.Y.S., Y.I.B., E.S.S., S.A.N., D.V.K.) Biological Faculty, Lomonosov Moscow State University, 119991 Moscow, Russia; Laboratory of Molecular Mechanisms of Immunity (A.V.B., S.A.N.), Engelhardt Institute of Molecular Biology, Russian Academy of Scien
  • Vanushko VE; Department of Immunology (P.V.B., A.V.B., Y.S.K., A.Y.S., Y.I.B., E.S.S., S.A.N., D.V.K.) Biological Faculty, Lomonosov Moscow State University, 119991 Moscow, Russia; Laboratory of Molecular Mechanisms of Immunity (A.V.B., S.A.N.), Engelhardt Institute of Molecular Biology, Russian Academy of Scien
  • Moshkovskii SA; Department of Immunology (P.V.B., A.V.B., Y.S.K., A.Y.S., Y.I.B., E.S.S., S.A.N., D.V.K.) Biological Faculty, Lomonosov Moscow State University, 119991 Moscow, Russia; Laboratory of Molecular Mechanisms of Immunity (A.V.B., S.A.N.), Engelhardt Institute of Molecular Biology, Russian Academy of Scien
  • Nedospasov SA; Department of Immunology (P.V.B., A.V.B., Y.S.K., A.Y.S., Y.I.B., E.S.S., S.A.N., D.V.K.) Biological Faculty, Lomonosov Moscow State University, 119991 Moscow, Russia; Laboratory of Molecular Mechanisms of Immunity (A.V.B., S.A.N.), Engelhardt Institute of Molecular Biology, Russian Academy of Scien
  • Kuprash DV; Department of Immunology (P.V.B., A.V.B., Y.S.K., A.Y.S., Y.I.B., E.S.S., S.A.N., D.V.K.) Biological Faculty, Lomonosov Moscow State University, 119991 Moscow, Russia; Laboratory of Molecular Mechanisms of Immunity (A.V.B., S.A.N.), Engelhardt Institute of Molecular Biology, Russian Academy of Scien
J Clin Endocrinol Metab ; 100(9): E1206-15, 2015 Sep.
Article in En | MEDLINE | ID: mdl-26196948
CONTEXT: Current methods of preoperative diagnostics frequently fail to discriminate between benign and malignant thyroid neoplasms. In encapsulated follicular-patterned tumors (EnFPT), this discrimination is challenging even using histopathological analysis. Autoantibody response against tumor-associated antigens is a well-documented phenomenon with prominent diagnostic potential; however, autoantigenicity of thyroid tumors remains poorly explored. OBJECTIVES: Objectives were exploration of tumor-associated antigen repertoire of thyroid tumors and identification of candidate autoantibody biomarkers capable of discrimination between benign and malignant thyroid neoplasms. DESIGN, SETTING, AND PATIENTS: Proteins isolated from FTC-133 cells were subjected to two-dimensional Western blotting using pooled serum samples of patients originally diagnosed with either papillary thyroid carcinoma (PTC) or EnFPT represented by apparently benign follicular thyroid adenomas, as well as healthy individuals. Immunoreactive proteins were identified using liquid chromatography-tandem mass-spectrometry. Pathological reassessment of EnFPT was performed applying nonconservative criteria for capsular invasion and significance of focal PTC nuclear changes (PTC-NCs). Recombinant T-complex protein 1 subunitζ (TCP-1ζ) was used to examine an expanded serum sample set of patients with various thyroid neoplasms (n = 89) for TCP-1ζ autoantibodies. All patients were included in tertiary referral centers. RESULTS: A protein demonstrating a distinct pattern of EnFPT-specific seroreactivity was identified as TCP-1ζ protein. A subsequent search for clinicopathological correlates of TCP-1ζ seroreactivity revealed nonclassical capsular invasion or focal PTC-NC in all TCP-1ζ antibody-positive cases. Further studies in an expanded sample set confirmed the specificity of TCP-1ζ autoantibodies to malignant EnFPT. CONCLUSIONS: We identified TCP-1ζ autoantibodies as a potential biomarker for presurgical discrimination between benign and malignant encapsulated follicular-patterned thyroid tumors. Our results suggest the use of nonconservative morphological criteria for diagnosis of malignant EnFPT in biomarker identification studies and provide a peculiar example of uncovering the diagnostic potential of a candidate biomarker using incorporation of pathological reassessment in the pipeline of immunoproteomic research.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Autoantibodies / Thyroid Neoplasms / Carcinoma, Papillary / Adenocarcinoma, Follicular / Chaperonin Containing TCP-1 Type of study: Prognostic_studies Limits: Adult / Female / Humans / Middle aged Language: En Journal: J Clin Endocrinol Metab Year: 2015 Document type: Article Country of publication: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Autoantibodies / Thyroid Neoplasms / Carcinoma, Papillary / Adenocarcinoma, Follicular / Chaperonin Containing TCP-1 Type of study: Prognostic_studies Limits: Adult / Female / Humans / Middle aged Language: En Journal: J Clin Endocrinol Metab Year: 2015 Document type: Article Country of publication: United States