{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T01:13:11Z","timestamp":1767921191569,"version":"3.49.0"},"reference-count":35,"publisher":"IMR Press","issue":"3","license":[{"start":{"date-parts":[[2022,3,8]],"date-time":"2022-03-08T00:00:00Z","timestamp":1646697600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Front. Biosci. (Landmark Ed)"],"abstract":"<jats:p>Background: Thyroid dysfunction, including hypothyroidism (THO) and hyperthyroidism (THE), commonly arise from pathological processes in the thyroid gland. The current diagnosis of thyroid dysfunction varies because of the age and sex of the patients. The aim of this study was to explore novel candidate biomarker panels for hypothyroidism and hyperthyroidism screening with mass spectrometry and bioinformatics. Methods: Plasma samples were collected from 15 THE patients, 9 THO patients, and 15 healthy controls. Data Independent Acquisition(DIA)-based proteomic and untargeted metabolomic analyses were performed to identify novel biomarker panels for THO and THE patients. Finally, three candidate biomarkers were verified by ELISA in 34 samples. Results: A total of 2738 proteins and 6103 metabolites were identified, and 173 proteins and 2487 metabolites were found to be differentially expressed among the THE, THO and control groups. The results of the ensemble feature selection, K-means clustering and least absolute shrinkage and selection operator (LASSO) regression model showed that two proteins (C4-A and C3\/C5 convertase) combined with two metabolites (L-arginine and L-proline), and proteins (APOL1 and ITIH4) combined with metabolites (cortisol, and cortisone) identified by plasma proteomics and metabolomics could help distinguish THO and THE patients from healthy controls, respectively. Conclusions: This study identified and verified two pairs of biomarker panels that can be used to distinguish THE and THO patients regardless of age and sex. Consequently, our findings represent a comprehensive analysis of thyroid dysfunction plasma, which is significant for clinical diagnosis.<\/jats:p>","DOI":"10.31083\/j.fbl2703090","type":"journal-article","created":{"date-parts":[[2022,3,18]],"date-time":"2022-03-18T09:28:02Z","timestamp":1647595682000},"source":"Crossref","is-referenced-by-count":10,"title":["Comparative Proteomic and Metabolomic Analyses of Plasma Reveal the Novel Biomarker Panels for Thyroid Dysfunction"],"prefix":"10.31083","volume":"27","author":[{"given":"Haodong","family":"Xia","sequence":"first","affiliation":[{"name":"The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, 310002 Hangzhou, Zhejiang, China"},{"name":"College of Biomedical Engineering and Instrument Science, Zhejiang University, 310027 Hangzhou, Zhejiang, China"},{"name":"Phase I Clinical Research Center, Zhejiang Provincial People\u2019s Hospital, 310014 Hangzhou, Zhejiang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaohan","family":"Li","sequence":"first","affiliation":[{"name":"College of Biomedical Engineering and Instrument Science, Zhejiang University, 310027 Hangzhou, Zhejiang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shengzhi","family":"Liu","sequence":"first","affiliation":[{"name":"College of Biomedical Engineering and Instrument Science, Zhejiang University, 310027 Hangzhou, Zhejiang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haote","family":"Han","sequence":"first","affiliation":[{"name":"The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, 310002 Hangzhou, Zhejiang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chaoting","family":"Zhou","sequence":"first","affiliation":[{"name":"School of Pharmacy, Zhejiang University of Technology, 310014 Hangzhou, Zhejiang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luyang","family":"Wang","sequence":"first","affiliation":[{"name":"School of Pharmacy, Hangzhou Medical College, 310059 Hangzhou, Zhejiang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiangan","family":"Jing","sequence":"first","affiliation":[{"name":"School of Pharmacy, Zhejiang University of Technology, 310014 Hangzhou, Zhejiang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingkui","family":"Tian","sequence":"first","affiliation":[{"name":"The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, 310002 Hangzhou, Zhejiang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiangmin","family":"Tong","sequence":"first","affiliation":[{"name":"Phase I Clinical Research Center, Zhejiang Provincial People\u2019s Hospital, 310014 Hangzhou, Zhejiang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Wang","sequence":"first","affiliation":[{"name":"Phase I Clinical Research Center, Zhejiang Provincial People\u2019s Hospital, 310014 Hangzhou, Zhejiang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Zhu","sequence":"first","affiliation":[{"name":"The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, 310002 Hangzhou, Zhejiang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"16242","published-online":{"date-parts":[[2022,3,8]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","unstructured":"Sinha RA, Singh BK, Yen PM. Direct effects of thyroid hormones on hepatic lipid metabolism. Nature Reviews Endocrinology. 2018; 14: 259\u2013269.","DOI":"10.1038\/nrendo.2018.10"},{"key":"ref2","doi-asserted-by":"crossref","unstructured":"Taylor PN, Albrecht D, Scholz A, Gutierrez-Buey G, Lazarus JH, Dayan CM, et al. Global epidemiology of hyperthyroidism and hypothyroidism. Nature Reviews Endocrinology. 2018; 14: 301\u2013316.","DOI":"10.1038\/nrendo.2018.18"},{"key":"ref3","doi-asserted-by":"crossref","unstructured":"Klein I, Danzi S. Thyroid Disease and the Heart. Current Problems in Cardiology. 2016; 41: 65\u201392.","DOI":"10.1016\/j.cpcardiol.2015.04.002"},{"key":"ref4","doi-asserted-by":"crossref","unstructured":"Alemu A, Terefe B, Abebe M, Biadgo B. Thyroid hormone dysfunction during pregnancy: A review. International Journal of Reproductive Biomedicine. 2016; 14: 677\u2013686.","DOI":"10.29252\/ijrm.14.11.677"},{"key":"ref5","doi-asserted-by":"crossref","unstructured":"Chaker L, Bianco AC, Jonklaas J, Peeters RP. Hypothyroidism. Lancet. 2017; 390: 1550\u20131562.","DOI":"10.1016\/S0140-6736(17)30703-1"},{"key":"ref6","doi-asserted-by":"crossref","unstructured":"Zhu WZ, Olson A, Portman M, Ledee D. Sex impacts cardiac function and the proteome response to thyroid hormone in aged mice. Proteome Science. 2020; 18: 11.","DOI":"10.1186\/s12953-020-00167-3"},{"key":"ref7","doi-asserted-by":"crossref","unstructured":"Ucal Y, Ozpinar A. Proteomics in thyroid cancer and other thyroid-related diseases: A review of the literature. Biochimica Et Biophysica Acta Proteins and Proteomics. 2020; 1868: 140510.","DOI":"10.1016\/j.bbapap.2020.140510"},{"key":"ref8","doi-asserted-by":"crossref","unstructured":"Coelho M, Raposo L, Goodfellow BJ, Atzori L, Jones J, Manadas B. The Potential of Metabolomics in the Diagnosis of Thyroid Cancer. International Journal of Molecular Sciences, 2020; 21: 5272.","DOI":"10.3390\/ijms21155272"},{"key":"ref9","doi-asserted-by":"crossref","unstructured":"Masood A, Benabdelkamel H, Ekhzaimy AA, Alfadda AA. Plasma-Based Proteomics Profiling of Patients with Hyperthyroidism after Antithyroid Treatment. Molecules, 2020; 25: 2831.","DOI":"10.3390\/molecules25122831"},{"key":"ref10","doi-asserted-by":"crossref","unstructured":"Alfadda AA, Benabdelkamel H, Masood A, Jammah AA, Ekhzaimy AA. Differences in the plasma proteome of patients with hypothyroidism before and after thyroid hormone replacement: A proteomic analysis. International Journal of Molecular Sciences, 2018; 19: 88.","DOI":"10.3390\/ijms19010088"},{"key":"ref11","doi-asserted-by":"crossref","unstructured":"Piras C, Pibiri M, Leoni VP, Balsamo A, Tronci L, Arisci N, et al. Analysis of metabolomics profile in hypothyroid patients before and after thyroid hormone replacement. Journal of Endocrinological Investigation. 2021; 44: 1309\u20131319.","DOI":"10.1007\/s40618-020-01434-y"},{"key":"ref12","doi-asserted-by":"crossref","unstructured":"Piras C, Arisci N, Poddighe S, Liggi S, Mariotti S, Atzori L. Metabolomic profile in hyperthyroid patients before and after antithyroid drug treatment: Correlation with thyroid hormone and TSH concentration. The International Journal of Biochemistry & Cell Biology. 2017; 93: 119\u2013128.","DOI":"10.1016\/j.biocel.2017.07.024"},{"key":"ref13","doi-asserted-by":"crossref","unstructured":"Liu J, Fu J, Jia Y, Yang N, Li J, Wang G. Serum Metabolomic Patterns in Patients with Autoimmune Thyroid Disease. Endocrine Practice. 2020; 26: 82\u201396.","DOI":"10.4158\/EP-2019-0162"},{"key":"ref14","unstructured":"Sun Z, Liu Y, Ouyang Q, Liu Z, Liu Y. Research progress of omics technology in the field of tumor resistance: From single-omics to multi-omics combination application. Journal of Central South University Medical Sciences, 2021; 46: 620\u2013627."},{"key":"ref15","doi-asserted-by":"crossref","unstructured":"Saraswat M, Joenv\u00e4\u00e4r\u00e4 S, Tohmola T, Sutinen E, Vartiainen V, Koli K, et al. Label-free plasma proteomics identifies haptoglobin-related protein as candidate marker of idiopathic pulmonary fibrosis and dysregulation of complement and oxidative pathways. Scientific Reports. 2020; 10: 7787.","DOI":"10.1038\/s41598-020-64759-x"},{"key":"ref16","doi-asserted-by":"crossref","unstructured":"Cox J, Mann M. MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification. Nature Biotechnology. 2008; 26: 1367\u20131372.","DOI":"10.1038\/nbt.1511"},{"key":"ref17","doi-asserted-by":"crossref","unstructured":"Choi M, Chang C, Clough T, Broudy D, Killeen T, MacLean B, et al. MSstats: an R package for statistical analysis of quantitative mass spectrometry-based proteomic experiments. Bioinformatics. 2014; 30: 2524\u20132526.","DOI":"10.1093\/bioinformatics\/btu305"},{"key":"ref18","doi-asserted-by":"crossref","unstructured":"von Mering C, Jensen LJ, Snel B, Hooper SD, Krupp M, Foglierini M, et al. STRING: known and predicted protein-protein associations, integrated and transferred across organisms. Nucleic Acids Research. 2005; 33: D433\u2013D437.","DOI":"10.1093\/nar\/gki005"},{"key":"ref19","doi-asserted-by":"crossref","unstructured":"Wozniak JM, Mills RH, Olson J, Caldera JR, Sepich-Poore GD, Carrillo-Terrazas M, et al. Mortality Risk Profiling of Staphylococcus aureus Bacteremia by Multi-omic Serum Analysis Reveals Early Predictive and Pathogenic Signatures. Cell. 2020; 182: 1311\u20131327.e14.","DOI":"10.1016\/j.cell.2020.07.040"},{"key":"ref20","doi-asserted-by":"crossref","unstructured":"Neumann U, Genze N, Heider D. EFS: an ensemble feature selection tool implemented as R-package and web-application. BioData Mining. 2017; 10: 21.","DOI":"10.1186\/s13040-017-0142-8"},{"key":"ref21","unstructured":"Kravets I. Hyperthyroidism: Diagnosis and Treatment. American Family Physician. 2016; 93: 363\u2013370."},{"key":"ref22","unstructured":"Rizzo LFL, Mana DL, Serra HA. Drug-induced hypothyroidism. Medicina. 2017; 77: 394\u2013404."},{"key":"ref23","doi-asserted-by":"crossref","unstructured":"Wang H, Liu M. Complement C4, infections, and autoimmune diseases. Frontiers in Immunology, 2021; 12: 2682.","DOI":"10.3389\/fimmu.2021.694928"},{"key":"ref24","doi-asserted-by":"crossref","unstructured":"Blanchin S, Estienne V, Durand-Gorde J, Carayon P, Ruf J. Complement activation by direct C4 binding to thyroperoxidase in Hashimoto\u2019s thyroiditis. Endocrinology. 2003; 144: 5422\u20135429.","DOI":"10.1210\/en.2003-0918"},{"key":"ref25","doi-asserted-by":"crossref","unstructured":"Yu H, Yang Y, Zhang M, Lu H, Zhang J, Wang H, et al. Thyroid status influence on adiponectin, acylation stimulating protein (ASP) and complement C3 in hyperthyroid and hypothyroid subjects. Nutrition & Metabolism. 2006; 3: 13.","DOI":"10.1186\/1743-7075-3-13"},{"key":"ref26","doi-asserted-by":"crossref","unstructured":"Jafarzadeh A, Poorgholami M, Izadi N, Nemati M, Rezayati M. Immunological and hematological changes in patients with hyperthyroidism or hypothyroidism. Clinical and Investigative Medicine Medecine Clinique Et Experimentale. 2010; 33: E271\u2013E279.","DOI":"10.25011\/cim.v33i5.14352"},{"key":"ref27","doi-asserted-by":"crossref","unstructured":"Albaugh VL, Pinzon-Guzman C, Barbul A. Arginine-Dual roles as an onconutrient and immunonutrient. Journal of Surgical Oncology. 2017; 115: 273\u2013280.","DOI":"10.1002\/jso.24490"},{"key":"ref28","doi-asserted-by":"crossref","unstructured":"Rodr\u00edguez-G\u00f3mez I, Moliz JN, Quesada A, Montoro-Molina S, Vargas-Tendero P, Osuna A, et al. L-Arginine metabolism in cardiovascular and renal tissue from hyper- and hypothyroid rats. Experimental Biology and Medicine. 2016; 241: 550\u2013556.","DOI":"10.1177\/1535370215619042"},{"key":"ref29","doi-asserted-by":"crossref","unstructured":"Wan G, Zhaorigetu S, Liu Z, Kaini R, Jiang Z, Hu CA. Apolipoprotein L1, a novel Bcl-2 homology domain 3-only lipid-binding protein, induces autophagic cell death. The Journal of Biological Chemistry. 2008; 283: 21540\u201321549.","DOI":"10.1074\/jbc.M800214200"},{"key":"ref30","doi-asserted-by":"crossref","unstructured":"Cubedo J, Padr\u00f3 T, Alonso R, Mata P, Badimon L. ApoL1 levels in high density lipoprotein and cardiovascular event presentation in patients with familial hypercholesterolemia. Journal of Lipid Research. 2016; 57: 1059\u20131073.","DOI":"10.1194\/jlr.P061598"},{"key":"ref31","doi-asserted-by":"crossref","unstructured":"Benvenga S, Alesci S, Trimarchi F. High-density lipoprotein-facilitated entry of thyroid hormones into cells: a mechanism different from the low-density lipoprotein-facilitated entry. Thyroid. 2002; 12: 547\u2013556.","DOI":"10.1089\/105072502320288384"},{"key":"ref32","doi-asserted-by":"crossref","unstructured":"Krisp C, Randall SA, McKay MJ, Molloy MP. Towards clinical applications of selected reaction monitoring for plasma protein biomarker studies. Proteomics Clinical Applications. 2012; 6: 42\u201359.","DOI":"10.1002\/prca.201100062"},{"key":"ref33","doi-asserted-by":"crossref","unstructured":"Ferrari E, Wittig A, Basilico F, Rossi R, De Palma A, Di Silvestre D, et al. Urinary Proteomics Profiles Are Useful for Detection of Cancer Biomarkers and Changes Induced by Therapeutic Procedures. Molecules. 2019; 24: 794.","DOI":"10.3390\/molecules24040794"},{"key":"ref34","doi-asserted-by":"crossref","unstructured":"Ohara N, Kobayashi M, Tuchida M, Koda R, Yoneoka Y, Iino N. Isolated Adrenocorticotropic Hormone Deficiency and Primary Hypothyroidism in a Patient Undergoing Long-Term Hemodialysis: A Case Report and Literature Review. The American Journal of Case Reports, 2020; 21: e922376.","DOI":"10.12659\/AJCR.922376"},{"key":"ref35","doi-asserted-by":"crossref","unstructured":"Mousa SS, Davis FB, Davis PJ, Mousa SA. Human Platelet Aggregation and Degranulation is Induced in Vitro by L-Thyroxine, but not by 3,5,3\u2032-Triiodo-L-Thyronine or Diiodothyropropionic Acid (DITPA). Clinical and Applied Thrombosis\/Hemostasis. 2010; 16: 288\u2013293.","DOI":"10.1177\/1076029609348315"}],"container-title":["Frontiers in Bioscience-Landmark"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.imrpress.com\/journal\/FBL\/27\/3\/10.31083\/j.fbl2703090","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,27]],"date-time":"2024-11-27T11:44:38Z","timestamp":1732707878000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.imrpress.com\/journal\/FBL\/27\/3\/10.31083\/j.fbl2703090"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,8]]},"references-count":35,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2022]]}},"alternative-id":["S2768-6701(22)00428-2"],"URL":"https:\/\/doi.org\/10.31083\/j.fbl2703090","relation":{},"ISSN":["2768-6701","2768-6698"],"issn-type":[{"value":"2768-6701","type":"print"},{"value":"2768-6698","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,8]]},"article-number":"90"}}