{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T05:31:27Z","timestamp":1786426287654,"version":"build-2736575974"},"reference-count":63,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100007777","name":"Tokyo University of Agriculture","doi-asserted-by":"publisher","award":["TUAGBG\u2010978132"],"award-info":[{"award-number":["TUAGBG\u2010978132"]}],"id":[{"id":"10.13039\/501100007777","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oral Diseases"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>We assessed protein biomarkers expressed in oral leukoplakia (OL) that are associated with the risk of transformation into oral squamous cell carcinoma (OSCC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Tissue sections of OL transforming into OSCC (leuko\u2010ca), the corresponding OSCC and OL that did not progress to OSCC (leuko\u2010nonca) were analyzed with global relative quantification to compare proteome profiles. Immunohistochemistry was performed to validate the expression of identified biomarkers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The top enriched biological pathways in OL transforming into OSCC within 5\u201326\u2009months after diagnosis (short duration [SD]\u2010leuko\u2010ca) compared with leuko\u2010nonca were pathways regulating remodeling of the extracellular matrix (ECM) and lipid and cholesterol metabolism\/transport. Kininogen\u20101, apolipoprotein E (ApoE), collagen alpha\u20101 (XVIII) chain (COL18A1), sortilin, and perlecan were the most downregulated proteins, whereas EEF1D was the most upregulated in SD\u2010leuko\u2010ca compared with leuko\u2010nonca. Immunohistochemistry confirmed the expression of kininogen\u20101, ApoE, perlecan, and EEF1D in OL and OSCC. In OSCC compared with leuko\u2010ca, enriched biological pathways involved keratinocyte and epithelial differentiation and immune response regulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We identified biomarkers in OL that were associated with the risk of malignant transformation. Our study gives further support for the importance of the immune system, ECM remodeling, and lipoproteins and cholesterol metabolism in the progression of OL to OSCC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/odi.70439","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T05:17:32Z","timestamp":1786425452000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Biomarkers Correlating With the Development of Oral Squamous Cell Carcinoma From Leukoplakia"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1349-9336","authenticated-orcid":false,"given":"Daniel","family":"Giglio","sequence":"first","affiliation":[{"name":"Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy University of Gothenburg  Gothenburg Sweden"},{"name":"Department of Medicine and Oncology Southern \u00c4lvsborg Hospital  Bor\u00e5s Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Divya","family":"Ganesh","sequence":"additional","affiliation":[{"name":"Department of Oral Medicine and Pathology, Institute of Odontology Sahlgrenska Academy at the University of Gothenburg  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bishwa Prakash","family":"Bhattarai","sequence":"additional","affiliation":[{"name":"Institute of Oral Biology University of Oslo  Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1687-3247","authenticated-orcid":false,"given":"Tine Merete","family":"S\u00f8land","sequence":"additional","affiliation":[{"name":"Institute of Oral Biology University of Oslo  Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas","family":"Sundberg","sequence":"additional","affiliation":[{"name":"Department of Oral Medicine and Pathology, Institute of Odontology Sahlgrenska Academy at the University of Gothenburg  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annika","family":"Thorsell","sequence":"additional","affiliation":[{"name":"Proteomics Core Facility Sahlgrenska Academy at the University of Gothenburg  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny","family":"\u00d6hman","sequence":"additional","affiliation":[{"name":"Department of Oral Medicine and Pathology, Institute of Odontology Sahlgrenska Academy at the University of Gothenburg  Gothenburg Sweden"},{"name":"Department of Clinical Pathology, Region V\u00e4stra G\u00f6taland Sahlgrenska University Hospital  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0061-825X","authenticated-orcid":false,"given":"Dipak","family":"Sapkota","sequence":"additional","affiliation":[{"name":"Institute of Oral Biology University of Oslo  Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3088-1550","authenticated-orcid":false,"given":"Bengt","family":"Hass\u00e9us","sequence":"additional","affiliation":[{"name":"Department of Oral Medicine and Pathology, Institute of Odontology Sahlgrenska Academy at the University of Gothenburg  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,10]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/froh.2025.1548829"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.4103\/jomfp.JOMFP_238_17"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/jop.13007"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.22034\/APJCP.2018.19.6.1639"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13277\u2010015\u20104629\u2010y"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2015.251"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010019\u20101056\u2010z"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1177\/00220345241266519"},{"issue":"1","key":"e_1_2_11_10_1","first-page":"3","article-title":"Histological and Immunochemical Studies of Oral Leukoplakia: Phenotype and Distribution of Immunocompetent Cells","volume":"47","author":"Bondad\u2010Palmario G. 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