{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T08:45:35Z","timestamp":1772268335962,"version":"3.50.1"},"reference-count":43,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2022,4,19]],"date-time":"2022-04-19T00:00:00Z","timestamp":1650326400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical University of Warsaw","award":["1WF\/NM1\/18"],"award-info":[{"award-number":["1WF\/NM1\/18"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The study was designed to evaluate the potential validity and utility of selected molecular markers in serum samples from patients with specific stages of laryngeal intraepithelial lesions that could serve as diagnostic tools in differentiation of benign and dysplastic lesions from invasive pathologies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Prospective study included 80 consecutive patients with vocal fold lesions treated at the single otorhinolaryngology centre. All participants had surgical resection of the lesion. Blood samples were collected from each patient before the surgery. Final diagnosis was confirmed on histopathological examination and included 39 (48.75%) non-dysplastic lesions, eight (10%) low-grade dysplasia, six (7.5%) high-grade dysplasia and 27 (33.75%) invasive cancers. The ELISA procedures were performed according to the manufacturer\u2019s instruction. Individual serum concentration of selected proteins was reported in ng\/ml: Vascular Endothelial-Cadherin Complex (VE-cad), CD44, Human High mobility group protein B1(HMGB1), Kallikrein 6.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The highest mean levels of HMGB1, KLK6 and VE-cad were detected in sera of patients with low-grade dysplasia (81.14, 24.33, 14.17 respectively). Soluble CD44 was the most elevated in patients with non-dysplastic lesions (2.49). The HMGB1, KLK6 and VE-cad serum levels were increasing from non-dysplastic to low-grade dysplasia and followed by the decrease for high-grade dysplasia and invasive cancer, however the differences were not significant (\n                      <jats:italic>p<\/jats:italic>\n                      -values 0.897, 0.354, 0.1 respectively). Patients\u2019 serum had the highest CD44 concentration in non-dysplastic and low-grade dysplasia with the following decrease through high-grade dysplasia and invasive cancer. GERD symptomatic patients had higher levels of KLK6 and CD44 than other patients (\n                      <jats:italic>p<\/jats:italic>\n                      -value 0.06 and 0.084 respectively). There were no significant differences of biomarkers levels related to patients\u2019 gender (\n                      <jats:italic>p<\/jats:italic>\n                      -value from 0.243 to 1) or smoking status (\n                      <jats:italic>p<\/jats:italic>\n                      -value from 0.22 to 0.706).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>VE-cad, HMGB1, CD44 and KLK6 did not prove to be reliable biomarkers implicating malignant potential within vocal fold hypertrophic intraepithelial lesions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.7717\/peerj.13104","type":"journal-article","created":{"date-parts":[[2022,4,19]],"date-time":"2022-04-19T05:40:55Z","timestamp":1650346855000},"page":"e13104","source":"Crossref","is-referenced-by-count":1,"title":["Serum expression of Vascular Endothelial-Cadherin, CD44, Human High mobility group B1, Kallikrein 6 proteins in different stages of laryngeal intraepithelial lesions and early glottis cancer"],"prefix":"10.7717","volume":"10","author":[{"given":"Micha\u0142","family":"\u017burek","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology Head and Neck Surgery, Medical University of Warsaw, Warsaw, Poland"},{"name":"Doctoral School, Medical University of Warsaw, Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Rzepakowska","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Head and Neck Surgery, Medical University of Warsaw, Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iwona","family":"Kotu\u0142a","sequence":"additional","affiliation":[{"name":"Department of Laboratory Diagnostics and Clinical Immunology of Developmental Age, Medical University of Warsaw, Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Urszula","family":"Demkow","sequence":"additional","affiliation":[{"name":"Department of Laboratory Diagnostics and Clinical Immunology of Developmental Age, Medical University of Warsaw, Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazimierz","family":"Niemczyk","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Head and Neck Surgery, Medical University of Warsaw, Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"4443","published-online":{"date-parts":[[2022,4,19]]},"reference":[{"issue":"2","key":"10.7717\/peerj.13104\/ref-1","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1007\/s10456-012-9260-6","article-title":"Clinical, pharmacokinetic and pharmacodynamic evaluations of metronomic UFT and cyclophosphamide plus celecoxib in patients with advanced refractory gastrointestinal cancers","volume":"15","author":"Allegrini","year":"2012","journal-title":"Angiogenesis"},{"issue":"5","key":"10.7717\/peerj.13104\/ref-2","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1016\/j.ejca.2004.10.031","article-title":"Molecular markers in laryngeal squamous cell carcinoma: towards an integrated clinicobiological approach","volume":"41","author":"Almadori","year":"2005","journal-title":"European Journal of Cancer"},{"issue":"6","key":"10.7717\/peerj.13104\/ref-3","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1177\/1358863X15591201","article-title":"Soluble vascular endothelial-cadherin and auto-antibodies to human vascular endothelial-cadherin in human diseases: two new biomarkers of endothelial dysfunction","volume":"20","author":"Blaise","year":"2015","journal-title":"Vascular Medicine"},{"issue":"11","key":"10.7717\/peerj.13104\/ref-4","doi-asserted-by":"publisher","first-page":"1835","DOI":"10.1016\/j.prp.2018.09.010","article-title":"The expression and biological information analysis of miR-375-3p in head and neck squamous cell carcinoma based on 1825 samples from GEO, TCGA, and peer-reviewed publications","volume":"214","author":"Cen","year":"2018","journal-title":"Pathology Research and Practice"},{"issue":"1","key":"10.7717\/peerj.13104\/ref-5","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1186\/1471-2407-14-15","article-title":"Significance of CD44 expression in head and neck cancer: a systemic review and meta-analysis","volume":"14","author":"Chen","year":"2014","journal-title":"BMC Cancer"},{"issue":"4","key":"10.7717\/peerj.13104\/ref-6","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1016\/j.otc.2008.01.016","article-title":"Laryngeal cancer: diagnosis and preoperative work-up","volume":"41","author":"Chu","year":"2008","journal-title":"Otolaryngologic Clinics of North America"},{"issue":"9","key":"10.7717\/peerj.13104\/ref-7","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1007\/s12032-014-0139-9","article-title":"Evaluation of soluble CD44 protein marker to distinguish the premalignant and malignant carcinoma cases in cervical cancer patients","volume":"31","author":"Dasari","year":"2014","journal-title":"Medical Oncology"},{"issue":"1","key":"10.7717\/peerj.13104\/ref-8","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1186\/s12885-015-1566-5","article-title":"Prognostic significance of multiple kallikreins in high-grade astrocytoma","volume":"15","author":"Drucker","year":"2015","journal-title":"BMC Cancer"},{"issue":"2","key":"10.7717\/peerj.13104\/ref-9","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1097\/PAP.0000000000000106","article-title":"Laryngeal squamous intraepithelial lesions: an updated review on etiology, classification, molecular changes, and treatment","volume":"23","author":"Gale","year":"2016","journal-title":"Advances in Anatomic Pathology"},{"issue":"1","key":"10.7717\/peerj.13104\/ref-10","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1007\/s12105-017-0788-z","article-title":"Update from the 4th Edition of the World Health Organization classification of head and neck tumours: what is new in the 2017 WHO Blue Book for tumours of the hypopharynx, larynx, trachea and parapharyngeal space","volume":"11","author":"Gale","year":"2017","journal-title":"Head and Neck Pathology"},{"key":"10.7717\/peerj.13104\/ref-11","article-title":"Larynx","author":"Globocan","year":"2020"},{"issue":"12","key":"10.7717\/peerj.13104\/ref-12","doi-asserted-by":"publisher","first-page":"1850","DOI":"10.3390\/biom11121850","article-title":"CD44: a multifunctional mediator of cancer progression","volume":"11","author":"Hassn Mesrati","year":"2021","journal-title":"Biomolecules"},{"issue":"2","key":"10.7717\/peerj.13104\/ref-13","doi-asserted-by":"publisher","first-page":"110","DOI":"10.4103\/jispcd.JISPCD_408_17","article-title":"The expression and functional significance of vascular endothelial-Cadherin, CD44, and Vimentin in oral squamous cell carcinoma","volume":"8","author":"Irani","year":"2018","journal-title":"Journal of International Society of Preventive and Community Dentistry"},{"issue":"11","key":"10.7717\/peerj.13104\/ref-14","doi-asserted-by":"publisher","first-page":"1349","DOI":"10.5858\/arpa.2014-0471-OA","article-title":"MicroRNA-375 suppresses extracellular matrix degradation and invadopodial activity in head and neck squamous cell carcinoma","volume":"139","author":"Jimenez","year":"2015","journal-title":"Archives of Pathology & Laboratory Medicine"},{"issue":"3","key":"10.7717\/peerj.13104\/ref-15","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.mam.2014.05.001","article-title":"HMGB1 in health and disease","volume":"40","author":"Kang","year":"2014","journal-title":"Molecular Aspects of Medicine"},{"issue":"9","key":"10.7717\/peerj.13104\/ref-16","doi-asserted-by":"publisher","first-page":"2635","DOI":"10.1002\/hed.26186","article-title":"Use of narrowband imaging for the diagnosis and screening of laryngeal cancer: a systematic review and meta-analysis","volume":"42","author":"Kim","year":"2020","journal-title":"Head & Neck"},{"issue":"8","key":"10.7717\/peerj.13104\/ref-17","doi-asserted-by":"publisher","first-page":"1366","DOI":"10.1097\/IGC.0000000000000781","article-title":"Diagnostic accuracy of serum kallikrein-related peptidases for ovarian cancer: a systematic review and meta-analysis","volume":"26","author":"Lan","year":"2016","journal-title":"International Journal of Gynecological Cancer"},{"issue":"4","key":"10.7717\/peerj.13104\/ref-18","doi-asserted-by":"publisher","first-page":"e34318","DOI":"10.1371\/journal.pone.0034318","article-title":"Diagnostic significance of serum HMGB1 in colorectal carcinomas","volume":"7","author":"Lee","year":"2012","journal-title":"PLOS ONE"},{"issue":"21","key":"10.7717\/peerj.13104\/ref-19","doi-asserted-by":"publisher","first-page":"34630","DOI":"10.18632\/oncotarget.16120","article-title":"A functional variant at the miRNA binding site in HMGB1 gene is associated with risk of oral squamous cell carcinoma","volume":"8","author":"Lin","year":"2017","journal-title":"Oncotarget"},{"issue":"1","key":"10.7717\/peerj.13104\/ref-20","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1158\/1055-9965.EPI-06-0602","article-title":"Early detection of head and neck cancer: development of a novel screening tool using multiplexed immunobead-based biomarker profiling","volume":"16","author":"Linkov","year":"2007","journal-title":"Cancer Epidemiology Biomarkers & Prevention"},{"issue":"6","key":"10.7717\/peerj.13104\/ref-21","doi-asserted-by":"publisher","first-page":"574","DOI":"10.3109\/00016489.2011.652308","article-title":"Potential prognostic and therapeutic role for angiogenesis markers in laryngeal carcinoma","volume":"132","author":"Lionello","year":"2012","journal-title":"Acta Oto-Laryngologica"},{"issue":"16","key":"10.7717\/peerj.13104\/ref-22","doi-asserted-by":"publisher","first-page":"3007","DOI":"10.1016\/j.ejca.2010.07.016","article-title":"Elevated expression of HMGB1 in squamous-cell carcinoma of the head and neck and its clinical significance","volume":"46","author":"Liu","year":"2010","journal-title":"European Journal of Cancer"},{"issue":"7","key":"10.7717\/peerj.13104\/ref-23","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/j.canlet.2019.10.010","article-title":"CD44(+) tumor cells promote early angiogenesis in head and neck squamous cell carcinoma","volume":"467","author":"Ludwig","year":"2019","journal-title":"Cancer Letters"},{"issue":"2","key":"10.7717\/peerj.13104\/ref-24","doi-asserted-by":"publisher","first-page":"267","DOI":"10.4103\/jomfp.JOMFP_246_18","article-title":"Structure, function and role of CD44 in neoplasia","volume":"23","author":"Mishra","year":"2019","journal-title":"Journal of Oral and Maxillofacial Pathology"},{"key":"10.7717\/peerj.13104\/ref-25","doi-asserted-by":"publisher","first-page":"261","DOI":"10.22038\/IJORL.2018.31383.2035","article-title":"Overexpression of high-mobility motor box 1 in the blood and tissues of patients with head and neck squamous cell carcinoma","volume":"30","author":"Mohajertehran","year":"2018","journal-title":"Iranian Journal of Otorhinolaryngology"},{"key":"10.7717\/peerj.13104\/ref-26","article-title":"The Cancer Genome Atlas Program","author":"National Cancer Institute","year":"2022"},{"issue":"04","key":"10.7717\/peerj.13104\/ref-27","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1055\/s-0036-1583168","article-title":"Clinical value of high mobility group box 1 and the receptor for advanced glycation end-products in head and neck cancer: a systematic review","volume":"20","author":"Nguyen","year":"2016","journal-title":"International Archives of Otorhinolaryngology"},{"issue":"1","key":"10.7717\/peerj.13104\/ref-28","doi-asserted-by":"publisher","first-page":"18","DOI":"10.21147\/j.issn.1000-9604.2020.01.03","article-title":"Updates on larynx cancer epidemiology","volume":"32","author":"Nocini","year":"2020","journal-title":"Chinese Journal of Cancer Research"},{"issue":"3","key":"10.7717\/peerj.13104\/ref-29","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1007\/s00404-015-3864-1","article-title":"Clinical impact of high mobility group box 1 protein in epithelial ovarian cancer","volume":"293","author":"Paek","year":"2016","journal-title":"Archives of Gynecology"},{"issue":"12","key":"10.7717\/peerj.13104\/ref-30","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1007\/s12032-014-0316-x","article-title":"Clinical value of serum HMGB1 in diagnosis and prognosis of laryngeal squamous cell carcinoma","volume":"31","author":"Qiu","year":"2014","journal-title":"Medical Oncology"},{"issue":"4","key":"10.7717\/peerj.13104\/ref-31","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1007\/s00405-011-1831-4","article-title":"Biomarkers predicting malignant progression of laryngeal epithelial precursor lesions: a systematic review","volume":"269","author":"Rodrigo","year":"2012","journal-title":"European Archives of Oto-Rhino-Laryngology"},{"key":"10.7717\/peerj.13104\/ref-32","doi-asserted-by":"publisher","first-page":"666895","DOI":"10.3389\/froh.2021.666895","article-title":"Vasculogenic mimicry in head and neck squamous cell carcinoma-time to take notice","volume":"2","author":"Salem","year":"2021","journal-title":"Frontiers in Oral Health"},{"issue":"10","key":"10.7717\/peerj.13104\/ref-33","doi-asserted-by":"publisher","first-page":"1790","DOI":"10.1016\/j.jprot.2010.01.013","article-title":"Protein biomarker discovery for head and neck cancer","volume":"73","author":"Schaaij-Visser","year":"2010","journal-title":"Journal of Proteomics"},{"issue":"1","key":"10.7717\/peerj.13104\/ref-34","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1186\/s12943-015-0381-6","article-title":"Kallikrein-related peptidase 6 regulates epithelial-to-mesenchymal transition and serves as prognostic biomarker for head and neck squamous cell carcinoma patients","volume":"14","author":"Schrader","year":"2015","journal-title":"Molecular Cancer"},{"issue":"11","key":"10.7717\/peerj.13104\/ref-35","doi-asserted-by":"publisher","first-page":"3059","DOI":"10.31557\/APJCP.2018.19.11.3059","article-title":"Comparison of salivary and serum soluble CD44 levels between patients with oral SCC and healthy controls","volume":"19","author":"Seyedmajidi","year":"2018","journal-title":"Asian Pacific Journal of Cancer Prevention"},{"issue":"6","key":"10.7717\/peerj.13104\/ref-36","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1159\/000445951","article-title":"Immunohistochemical expression and serum levels of CD44 as prognostic indicators in patients with non-small cell lung cancer","volume":"90","author":"Shinohara","year":"2016","journal-title":"Oncology"},{"issue":"1","key":"10.7717\/peerj.13104\/ref-37","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1177\/030089160609200111","article-title":"Levels of VE-cadherin increase independently of VEGF in preoperative sera of patients with colorectal cancer","volume":"92","author":"Sulkowska","year":"2006","journal-title":"Tumori Journal"},{"issue":"25","key":"10.7717\/peerj.13104\/ref-38","doi-asserted-by":"publisher","first-page":"17876","DOI":"10.18632\/oncotarget.24947","article-title":"Diagnostic and prognostic biomarker potential of kallikrein family genes in different cancer types","volume":"9","author":"Tailor","year":"2018","journal-title":"Oncotarget"},{"issue":"7","key":"10.7717\/peerj.13104\/ref-39","doi-asserted-by":"publisher","first-page":"1028","DOI":"10.1016\/j.yexcr.2013.01.013","article-title":"Inherent phenotypic plasticity facilitates progression of head and neck cancer: endotheliod characteristics enable angiogenesis and invasion","volume":"319","author":"Tong","year":"2013","journal-title":"Experimental Cell Research"},{"issue":"4","key":"10.7717\/peerj.13104\/ref-40","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1177\/0194599820957251","article-title":"Biomarkers for malignant potential in vocal fold leukoplakia: a state of the art review","volume":"164","author":"Wan","year":"2021","journal-title":"Otolaryngology\u2013Head and Neck Surgery"},{"issue":"5","key":"10.7717\/peerj.13104\/ref-41","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1016\/j.oraloncology.2011.12.009","article-title":"HMGB1 is overexpressed in tumor cells and promotes activity of regulatory T cells in patients with head and neck cancer","volume":"48","author":"Wild","year":"2012","journal-title":"Oral Oncology"},{"issue":"31","key":"10.7717\/peerj.13104\/ref-42","doi-asserted-by":"publisher","first-page":"50417","DOI":"10.18632\/oncotarget.10413","article-title":"HMGB1 overexpression as a prognostic factor for survival in cancer: a meta-analysis and systematic review","volume":"7","author":"Wu","year":"2016","journal-title":"Oncotarget"},{"issue":"4","key":"10.7717\/peerj.13104\/ref-43","doi-asserted-by":"publisher","first-page":"594093","DOI":"10.1155\/2014\/594093","article-title":"Identification of human tissue kallikrein 6 as a potential marker of laryngeal cancer based on the relevant secretory\/releasing protein database","volume":"2014","author":"Zhang","year":"2014","journal-title":"Disease Markers"}],"container-title":["PeerJ"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/peerj.com\/articles\/13104.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/peerj.com\/articles\/13104.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/peerj.com\/articles\/13104.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/peerj.com\/articles\/13104.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,19]],"date-time":"2022-04-19T05:41:04Z","timestamp":1650346864000},"score":1,"resource":{"primary":{"URL":"https:\/\/peerj.com\/articles\/13104"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,19]]},"references-count":43,"alternative-id":["10.7717\/peerj.13104"],"URL":"https:\/\/doi.org\/10.7717\/peerj.13104","archive":["CLOCKSS","LOCKSS","Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.7287\/peerj.13104v0.1\/reviews\/3","asserted-by":"object"},{"id-type":"doi","id":"10.7287\/peerj.13104v0.1\/reviews\/2","asserted-by":"object"},{"id-type":"doi","id":"10.7287\/peerj.13104v0.1\/reviews\/1","asserted-by":"object"},{"id-type":"doi","id":"10.7287\/peerj.13104v0.2\/reviews\/3","asserted-by":"object"},{"id-type":"doi","id":"10.7287\/peerj.13104v0.2\/reviews\/2","asserted-by":"object"}]},"ISSN":["2167-8359"],"issn-type":[{"value":"2167-8359","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,19]]},"article-number":"e13104"}}