{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T16:19:29Z","timestamp":1772986769656,"version":"3.50.1"},"reference-count":35,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T00:00:00Z","timestamp":1750118400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T00:00:00Z","timestamp":1750118400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pathology International"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The glycoform of heart development protein with EGF\u2010like domains 1 (HEG1) recognized by the SKM9\u20102 monoclonal antibody is a useful diagnostic marker for malignant pleural mesothelioma (MPM). The putative glycoform includes core 2\n                    <jats:italic>O<\/jats:italic>\n                    \u2010glycans carrying sialyl poly\u2010\n                    <jats:italic>N<\/jats:italic>\n                    \u2010acetyllactosamine (LacNAc), but sulfation modifications are undetermined. Since sialyl 6\u2010sulfo LacNAc\u2010capped core 2\n                    <jats:italic>O<\/jats:italic>\n                    \u2010glycans are expressed in MPM and their structure overlaps with low\u2010sulfated keratan sulfate (KS), we asked whether low\u2010sulfated KS is expressed in MPM and whether HEG1 is decorated with low\u2010sulfated KS. We performed immunohistochemical analysis of 41 MPM cases using anti\u2010KS monoclonal antibodies and endoglycosidases, reversed\u2010phase ion\u2010pair high\u2010performance liquid chromatography analysis of KS\/sulfated LacNAc isolated from human pleural tissue, and western blot analysis of HEG1\u00b7IgG recombinant fusion proteins secreted from low\u2010sulfated KS\u2010expressing human embryonic kidney cells. Most MPM tissues were stained with anti\u2010low\u2010sulfated KS antibodies and staining was eliminated by endo\u2010\u03b2\u2010galactosidase and keratanase II but not by peptide\u2010\n                    <jats:italic>N<\/jats:italic>\n                    \u2010glycosidase F. Disaccharide composition analysis revealed that mono\u2010sulfated LacNAc disaccharide and di\u2010sulfated LacNAc disaccharide accounted for 83.1% and 16.9% of pleural KS\/sulfated LacNAc, respectively. Western blot analysis of HEG1\u00b7IgG glycoforms indicated that HEG1 functions as a core protein for low\u2010sulfated KS. Thus, HEG1 protein decorated with low\u2010sulfated KS is expressed in MPM.\n                  <\/jats:p>","DOI":"10.1111\/pin.70033","type":"journal-article","created":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T07:55:26Z","timestamp":1750146926000},"page":"504-512","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Expression of Heart Development Protein With EGF\u2010Like Domains 1 (HEG1) Decorated With Low\u2010Sulfated Keratan Sulfate in Human Malignant Pleural Mesothelioma"],"prefix":"10.1111","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2818-6703","authenticated-orcid":false,"given":"Koki","family":"Nakashima","sequence":"first","affiliation":[{"name":"Department of Pathology, Faculty of Medical Sciences University of Fukui Eiheiji Japan"},{"name":"Department of Respiratory Medicine, Faculty of Medical Sciences University of Fukui Eiheiji 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