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It is confirmed mainly by fine-needle aspiration biopsy (FNAB), an invasive diagnostic method. The key proteins responsible for thyroid hormone biosynthesis are glycosylated. Hence, changes in site-specific glycosylation are associated with thyroid cancer. Integrated quantitative proteomic and glycoproteomic analyses of body fluids from patients with PTC may identify potential noninvasive biomarkers, improve diagnostic accuracy, and elucidate the basic mechanisms of tumor development. In the present study, we demonstrate an integrated, highly reproducible, rapid method involving body fluid proteome and glycoproteome analysis. Moreover, this method may quantitatively profile protein glycosylation. Intact N-glycopeptides from the urine and plasma of healthy controls (HC), PTC, and PTC with Hashimoto\u2019s thyroiditis (PHT) were enriched by hydrophilic interaction liquid chromatography. Sialic acid was removed from the N-glycopeptides with trifluoroacetic acid and heat. The desialo-N-glycopeptides were analyzed by HCD-MS\/MS using stepped collision energies and several search engines for quantitative profiling. Ninety-two altered proteins and 134 intact N-glycopeptides were isolated from the plasma and urine samples of the three groups (90 samples from 15 subjects). To the best of our knowledge, this study is the first to compare the plasma and urinary proteomes and glycoproteomes of HC, PTC, and PHT. Moreover, we reveal a novel indicator (ratio of fucosylated to nonfucosylated N-glycopeptide or F\/NF) through desialo-N-glycopeptide analysis. These differently expressed glycoproteins and F\/NF may serve as biomarkers contributing to clinical cancer diagnostics and could be used to improve diagnostic accuracy noninvasively.<\/jats:p>","DOI":"10.1021\/acs.jproteome.9b00672","type":"journal-article","created":{"date-parts":[[2019,12,4]],"date-time":"2019-12-04T13:35:06Z","timestamp":1575466506000},"page":"2539-2552","source":"Crossref","is-referenced-by-count":32,"title":["Comparative\nGlycoproteomic Profiling of Human Body\nFluid between Healthy Controls and Patients with Papillary Thyroid\nCarcinoma"],"prefix":"10.1021","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0513-8941","authenticated-orcid":true,"given":"Yong","family":"Zhang","sequence":"first","affiliation":[{"name":"West China Hospital, Sichuan University , , ,","place":["Chengdu, China, 610041"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanjun","family":"Zhao","sequence":"additional","affiliation":[{"name":"West China Hospital, Sichuan University , , ,","place":["Chengdu, China, 610041"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Zhao","sequence":"additional","affiliation":[{"name":"National Institute of Metrology , , ,","place":["Beijing, China, 102206"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonghong","family":"Mao","sequence":"additional","affiliation":[{"name":"West China Hospital, Sichuan University , , ,","place":["Chengdu, China, 610041"]},{"name":"West China Hospital, Sichuan University , , ,","place":["Chengdu, China, 610041"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Su","sequence":"additional","affiliation":[{"name":"West China Hospital, Sichuan University , , ,","place":["Chengdu, China, 610041"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Zhong","sequence":"additional","affiliation":[{"name":"West China Hospital, Sichuan University , , ,","place":["Chengdu, China, 610041"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shisheng","family":"Wang","sequence":"additional","affiliation":[{"name":"West China Hospital, Sichuan University , , ,","place":["Chengdu, China, 610041"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Zhai","sequence":"additional","affiliation":[{"name":"National Institute of Metrology , , ,","place":["Beijing, China, 102206"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingqiu","family":"Cheng","sequence":"additional","affiliation":[{"name":"West China Hospital, Sichuan University , , ,","place":["Chengdu, China, 610041"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1960-4862","authenticated-orcid":true,"given":"Xiang","family":"Fang","sequence":"additional","affiliation":[{"name":"National Institute of Metrology , , ,","place":["Beijing, China, 102206"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingqiang","family":"Zhu","sequence":"additional","affiliation":[{"name":"West China Hospital, Sichuan University , , ,","place":["Chengdu, China, 610041"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2214-9474","authenticated-orcid":true,"given":"Hao","family":"Yang","sequence":"additional","affiliation":[{"name":"West China Hospital, Sichuan University , , ,","place":["Chengdu, China, 610041"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2019,12,4]]},"reference":[{"issue":"2","key":"2026081714242452700_cit1","doi-asserted-by":"publisher","first-page":"468","DOI":"10.1016\/j.bbcan.2014.09.002","article-title":"Familial nonmedullary\nthyroid cancer: Screening, clinical, molecular and genetic findings","volume":"1846","author":"Navas-Carrillo","year":"2014","journal-title":"Biochim. Biophys. Acta, Rev. Cancer"},{"issue":"10061","key":"2026081714242452700_cit2","doi-asserted-by":"publisher","first-page":"2783","DOI":"10.1016\/S0140-6736(16)30172-6","article-title":"Thyroid cancer","volume":"388","author":"Cabanillas","year":"2016","journal-title":"Lancet"},{"issue":"2","key":"2026081714242452700_cit3","doi-asserted-by":"publisher","first-page":"303","DOI":"10.4143\/crt.2018.143","article-title":"Cancer\nStatistics in Korea: Incidence, Mortality, Survival, and Prevalence\nin 2015","volume":"50","author":"Jung","year":"2018","journal-title":"Cancer Res. Treat."},{"issue":"3","key":"2026081714242452700_cit4","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1016\/j.critrevonc.2013.12.007","article-title":"An update on molecular\nbiology of thyroid cancers","volume":"90","author":"Omur","year":"2014","journal-title":"Crit Rev. 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Pathol."},{"issue":"1","key":"2026081714242452700_cit7","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1186\/s12885-017-3104-0","article-title":"Thyroid fine-needle\naspiration biopsy positively correlates with increased diagnosis of\nthyroid cancer in South Korean patients","volume":"17","author":"Cho","year":"2017","journal-title":"BMC\nCancer"},{"issue":"11","key":"2026081714242452700_cit8","doi-asserted-by":"publisher","first-page":"1535","DOI":"10.1089\/thy.2016.0075","article-title":"Thyroid Cancer Screening in South\nKorea Increases Detection of Papillary Cancers with No Impact on Other\nSubtypes or Thyroid Cancer Mortality","volume":"26","author":"Ahn","year":"2016","journal-title":"Thyroid"},{"issue":"1","key":"2026081714242452700_cit9","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1002\/cncy.20124","article-title":"Improved preoperative\ndefinitive diagnosis of papillary thyroid carcinoma in FNAs prepared\nwith both ThinPrep and conventional smears compared with FNAs prepared\nwith Thin Prep alone","volume":"119","author":"Luu","year":"2011","journal-title":"Cancer Cytopathol."},{"issue":"4","key":"2026081714242452700_cit10","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1159\/000339959","article-title":"The Bethesda System\nfor Reporting Thyroid Cytopathology:\na meta-analysis","volume":"56","author":"Bongiovanni","year":"2012","journal-title":"Acta Cytol."},{"issue":"11","key":"2026081714242452700_cit11","doi-asserted-by":"publisher","first-page":"1215","DOI":"10.1089\/thy.2009.0155","article-title":"The Bethesda\nthyroid fine-needle aspiration classification system: year 1 at an\nacademic institution","volume":"19","author":"Theoharis","year":"2009","journal-title":"Thyroid"},{"issue":"6","key":"2026081714242452700_cit12","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1002\/dc.21406","article-title":"A valuable adjunct\nto FNA diagnosis of papillary thyroid carcinoma: in-house PCR assay\nfor BRAF T1799A (V600E)","volume":"39","author":"Kucukodaci","year":"2011","journal-title":"Diagnostic cytopathology"},{"issue":"10","key":"2026081714242452700_cit13","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1038\/nrendo.2011.142","article-title":"Molecular\ngenetics and diagnosis of thyroid cancer","volume":"7","author":"Nikiforov","year":"2011","journal-title":"Nat.\nRev. 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Endocrinol."},{"issue":"2","key":"2026081714242452700_cit19","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1530\/ERC-13-0291","article-title":"Is BRAFV600E mutation\na marker for central nodal metastasis\nin small papillary thyroid carcinoma?","volume":"21","author":"Lang","year":"2014","journal-title":"Endocr.-Relat.\nCancer"},{"issue":"7747","key":"2026081714242452700_cit20","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1038\/s41586-019-0987-8","article-title":"Proteomics\nidentifies new therapeutic targets of early-stage hepatocellular carcinoma","volume":"567","author":"Jiang","year":"2019","journal-title":"Nature"},{"issue":"7758","key":"2026081714242452700_cit21","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1038\/s41586-019-1173-8","article-title":"Proteomics reveals NNMT as a master\nmetabolic regulator of cancer-associated fibroblasts","volume":"569","author":"Eckert","year":"2019","journal-title":"Nature"},{"issue":"7754","key":"2026081714242452700_cit22","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1038\/s41586-019-1130-6","article-title":"Targeting LIF-mediated paracrine\ninteraction for pancreatic cancer therapy and monitoring","volume":"569","author":"Shi","year":"2019","journal-title":"Nature"},{"issue":"7\u20138","key":"2026081714242452700_cit23","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1080\/10408363.2017.1394266","article-title":"High-resolution\nproteomics and metabolomics in thyroid cancer: Deciphering novel biomarkers","volume":"54","author":"Navas-Carrillo","year":"2017","journal-title":"Crit. 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