Evidence map›Paper›PMID 40525709›Full record

ArticlePathology international2025

Expression of Heart Development Protein With EGF-Like Domains 1 (HEG1) Decorated With Low-Sulfated Keratan Sulfate in Human Malignant Pleural Mesothelioma.

Koki Nakashima, Hitomi Hoshino, Zui Zhang, Tomoya O Akama, Nobuyuki Kondo, Seiki Hasegawa, Yoshitaka Sekido, Mana Fukushima, Tamotsu Ishizuka, Motohiro Kobayashi

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In one paragraph

Article in Pathology international, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Koki NakashimaDepartment of Pathology, Faculty of Medical Sciences, University of Fukui, Eiheiji, Japan.ORCID https://orcid.org/0000-0002-2818-6703
Hitomi HoshinoDepartment of Pathology, Faculty of Medical Sciences, University of Fukui, Eiheiji, Japan.
Zui ZhangDepartment of Biochemistry, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Tomoya O AkamaDepartment of Pharmacology, Kansai Medical University, Hirakata, Japan.
Nobuyuki KondoDivision of Thoracic Surgery, Department of Surgery, Hyogo College of Medicine, Nishinomiya, Japan.
Seiki HasegawaDivision of Thoracic Surgery, Department of Surgery, Hyogo College of Medicine, Nishinomiya, Japan.
Yoshitaka SekidoDivision of Cancer Biology, Aichi Cancer Center Research Institute, Nagoya, Japan.
Mana FukushimaDepartment of Pathology, Faculty of Medical Sciences, University of Fukui, Eiheiji, Japan.
Tamotsu IshizukaDepartment of Respiratory Medicine, Faculty of Medical Sciences, University of Fukui, Eiheiji, Japan.
Motohiro KobayashiDepartment of Pathology, Faculty of Medical Sciences, University of Fukui, Eiheiji, Japan.ORCID https://orcid.org/0000-0002-7607-0801

Funding

This study was supported in part by a Grant-in-Aid for Scientific Research (B) 21H02702 from the Japan Society for the Promotion of Science (to M.K.).
6 · The paper itself

Abstract

The glycoform of heart development protein with EGF-like domains 1 (HEG1) recognized by the SKM9-2 monoclonal antibody is a useful diagnostic marker for malignant pleural mesothelioma (MPM). The putative glycoform includes core 2 O-glycans carrying sialyl poly-N-acetyllactosamine (LacNAc), but sulfation modifications are undetermined. Since sialyl 6-sulfo LacNAc-capped core 2 O-glycans are expressed in MPM and their structure overlaps with low-sulfated keratan sulfate (KS), we asked whether low-sulfated KS is expressed in MPM and whether HEG1 is decorated with low-sulfated KS. We performed immunohistochemical analysis of 41 MPM cases using anti-KS monoclonal antibodies and endoglycosidases, reversed-phase ion-pair high-performance liquid chromatography analysis of KS/sulfated LacNAc isolated from human pleural tissue, and western blot analysis of HEG1·IgG recombinant fusion proteins secreted from low-sulfated KS-expressing human embryonic kidney cells. Most MPM tissues were stained with anti-low-sulfated KS antibodies and staining was eliminated by endo-β-galactosidase and keratanase II but not by peptide-N-glycosidase F. Disaccharide composition analysis revealed that mono-sulfated LacNAc disaccharide and di-sulfated LacNAc disaccharide accounted for 83.1% and 16.9% of pleural KS/sulfated LacNAc, respectively. Western blot analysis of HEG1·IgG glycoforms indicated that HEG1 functions as a core protein for low-sulfated KS. Thus, HEG1 protein decorated with low-sulfated KS is expressed in MPM.

Indexed as

Biomarkers, TumorKeratan SulfateLung NeoplasmsMesotheliomaPleural NeoplasmsAgedFemaleHumansImmunohistochemistryMaleMesothelioma, MalignantMiddle AgedBiomarkers, TumorKeratan Sulfateheart development protein with EGF‐like domains 1 (HEG1)low‐sulfated keratan sulfatemalignant pleural mesotheliomaprotein glycosylation

Identifiers

PMID40525709
PMCPMC12558675

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.