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Protein Signatures of Parathyroid Carcinomas Using Proteomic Analyses

Parathyroid carcinomas are rare endocrine tumors derived from the parathyroid glands with poor prognosis. Moreover, parathyroid carcinomas are resistant to radiation or drug therapy, and surgical resection is the only treatment option. Understanding the molecular pathogenesis of parathyroid carcinom...

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Autores principales: Kong, Sung Hye, Kim, Jung Hee, Han, Do-Hyun Han, Bae, Jeong Mo, Hong, Namki, Lee, Joon-Hyop, Park, So Young, Choi, Yong Jun, Lee, Sihoon, Rhee, Yumie, Kim, Sang Wan, Shin, Chan Soo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8089154/
http://dx.doi.org/10.1210/jendso/bvab048.2109
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author Kong, Sung Hye
Kim, Jung Hee
Han, Do-Hyun Han
Bae, Jeong Mo
Hong, Namki
Lee, Joon-Hyop
Park, So Young
Choi, Yong Jun
Lee, Sihoon
Rhee, Yumie
Kim, Sang Wan
Shin, Chan Soo
author_facet Kong, Sung Hye
Kim, Jung Hee
Han, Do-Hyun Han
Bae, Jeong Mo
Hong, Namki
Lee, Joon-Hyop
Park, So Young
Choi, Yong Jun
Lee, Sihoon
Rhee, Yumie
Kim, Sang Wan
Shin, Chan Soo
author_sort Kong, Sung Hye
collection PubMed
description Parathyroid carcinomas are rare endocrine tumors derived from the parathyroid glands with poor prognosis. Moreover, parathyroid carcinomas are resistant to radiation or drug therapy, and surgical resection is the only treatment option. Understanding the molecular pathogenesis of parathyroid carcinomas may pave the way for early diagnostic biomarkers and therapeutic targets. Therefore, we aimed to elucidate the protein signatures for parathyroid carcinomas through quantitative proteomic analyses. We performed liquid chromatography with tandem mass spectrometry (LC-MS/MS) technique with formalin-fixed paraffin-embedded (FFPE) samples and reached a quantitative depth of more than 5,000 proteins per sample. For the analyses, 23 parathyroid carcinoma and 15 adenoma samples were collected from five tertiary hospitals in Korea. Patients’ mean age was 52 years, and 24 (63%) were female. Patients with parathyroid carcinoma had higher parathyroid hormone (PTH) and serum calcium level than adenomas (PTH, 1077.6 ± 760.7, 181.8 ± 139.8 pg/mL; calcium 13.0 ± 2.8, 11.3 ± 1.0 mg/dL, respectively). From the proteomic expression profiling, there were 137 differentially expressed proteins with the cutoff of both p <0.05 and fold change > 1.5. Using the Ingenuity Pathway Analysis (IPA), top enriched canonical pathways in parathyroid carcinomas included glycoprotein-6 signaling related to the coagulation pathway, acute phase response, mTOR, and clathrin-/caveolar-mediated endocytosis signaling. In transcription factor analysis, TGFβ and TP53 were activated in carcinoma, and these factors were up-regulators of CD44 antigen and Annexin A2 (ANXA2) proteins. In network analysis, α-1-acid glycoprotein 1 (ORM1), laminin subunit β-2 (LAMB2), and Serpin family (SERPIN) proteins were derived as essential proteins and correlated to the AKT complex. Also, with the support vector machine (SVM)-based classification method, we derived a set of proteins that can discriminate carcinomas from adenomas, which consists of Carbonic anhydrase 4 (CA4), α/β hydrolase domain-containing protein 14B (ABHD14B), CD44, LAMB2, phosphatidylinositol transfer protein β isoform (PITPNB), and ORM1, with the lowest error rate of 11.1%. In conclusion, from the proteomics analyses of parathyroid neoplasms, newly recognized pathways - signaling related to coagulation, acute phase response, and endocytosis - were enriched in parathyroid carcinoma in addition to the known mTOR signaling pathway. The proteins such as α-1-acid glycoprotein and laminin subunit β-2 from SVM classification and network analyses could be the distinctive signature of carcinoma and may provide insights into the therapeutic target.
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spelling pubmed-80891542021-05-06 Protein Signatures of Parathyroid Carcinomas Using Proteomic Analyses Kong, Sung Hye Kim, Jung Hee Han, Do-Hyun Han Bae, Jeong Mo Hong, Namki Lee, Joon-Hyop Park, So Young Choi, Yong Jun Lee, Sihoon Rhee, Yumie Kim, Sang Wan Shin, Chan Soo J Endocr Soc Tumor Biology Parathyroid carcinomas are rare endocrine tumors derived from the parathyroid glands with poor prognosis. Moreover, parathyroid carcinomas are resistant to radiation or drug therapy, and surgical resection is the only treatment option. Understanding the molecular pathogenesis of parathyroid carcinomas may pave the way for early diagnostic biomarkers and therapeutic targets. Therefore, we aimed to elucidate the protein signatures for parathyroid carcinomas through quantitative proteomic analyses. We performed liquid chromatography with tandem mass spectrometry (LC-MS/MS) technique with formalin-fixed paraffin-embedded (FFPE) samples and reached a quantitative depth of more than 5,000 proteins per sample. For the analyses, 23 parathyroid carcinoma and 15 adenoma samples were collected from five tertiary hospitals in Korea. Patients’ mean age was 52 years, and 24 (63%) were female. Patients with parathyroid carcinoma had higher parathyroid hormone (PTH) and serum calcium level than adenomas (PTH, 1077.6 ± 760.7, 181.8 ± 139.8 pg/mL; calcium 13.0 ± 2.8, 11.3 ± 1.0 mg/dL, respectively). From the proteomic expression profiling, there were 137 differentially expressed proteins with the cutoff of both p <0.05 and fold change > 1.5. Using the Ingenuity Pathway Analysis (IPA), top enriched canonical pathways in parathyroid carcinomas included glycoprotein-6 signaling related to the coagulation pathway, acute phase response, mTOR, and clathrin-/caveolar-mediated endocytosis signaling. In transcription factor analysis, TGFβ and TP53 were activated in carcinoma, and these factors were up-regulators of CD44 antigen and Annexin A2 (ANXA2) proteins. In network analysis, α-1-acid glycoprotein 1 (ORM1), laminin subunit β-2 (LAMB2), and Serpin family (SERPIN) proteins were derived as essential proteins and correlated to the AKT complex. Also, with the support vector machine (SVM)-based classification method, we derived a set of proteins that can discriminate carcinomas from adenomas, which consists of Carbonic anhydrase 4 (CA4), α/β hydrolase domain-containing protein 14B (ABHD14B), CD44, LAMB2, phosphatidylinositol transfer protein β isoform (PITPNB), and ORM1, with the lowest error rate of 11.1%. In conclusion, from the proteomics analyses of parathyroid neoplasms, newly recognized pathways - signaling related to coagulation, acute phase response, and endocytosis - were enriched in parathyroid carcinoma in addition to the known mTOR signaling pathway. The proteins such as α-1-acid glycoprotein and laminin subunit β-2 from SVM classification and network analyses could be the distinctive signature of carcinoma and may provide insights into the therapeutic target. Oxford University Press 2021-05-03 /pmc/articles/PMC8089154/ http://dx.doi.org/10.1210/jendso/bvab048.2109 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Tumor Biology
Kong, Sung Hye
Kim, Jung Hee
Han, Do-Hyun Han
Bae, Jeong Mo
Hong, Namki
Lee, Joon-Hyop
Park, So Young
Choi, Yong Jun
Lee, Sihoon
Rhee, Yumie
Kim, Sang Wan
Shin, Chan Soo
Protein Signatures of Parathyroid Carcinomas Using Proteomic Analyses
title Protein Signatures of Parathyroid Carcinomas Using Proteomic Analyses
title_full Protein Signatures of Parathyroid Carcinomas Using Proteomic Analyses
title_fullStr Protein Signatures of Parathyroid Carcinomas Using Proteomic Analyses
title_full_unstemmed Protein Signatures of Parathyroid Carcinomas Using Proteomic Analyses
title_short Protein Signatures of Parathyroid Carcinomas Using Proteomic Analyses
title_sort protein signatures of parathyroid carcinomas using proteomic analyses
topic Tumor Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8089154/
http://dx.doi.org/10.1210/jendso/bvab048.2109
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