Loss of mucosal tolerance to glycoprotein 2 isoform 1 is a potential novel diagnostic biomarker for cholangiocarcinoma

Chang-Sheng Xia; Marcin Krawczyk; Chun Di; Łukasz Krupa; Beata Kruk; Piotr Krawczyk; Piotr Milkiewicz; Huizhang Bao; Xiao He; Damin Liu; Chunhong Fan; Abdullah Nasser; Steffi Lopens; Frank Ulrich Weiss; Fabian Frost; Peter Schierack; Dirk Roggenbuck; Yudong Liu

doi:10.1016/j.dld.2024.05.027

Loss of mucosal tolerance to glycoprotein 2 isoform 1 is a potential novel diagnostic biomarker for cholangiocarcinoma

Dig Liver Dis. 2024 Jun 8:S1590-8658(24)00785-0. doi: 10.1016/j.dld.2024.05.027. Online ahead of print.

Authors

Chang-Sheng Xia¹, Marcin Krawczyk², Chun Di¹, Łukasz Krupa³, Beata Kruk⁴, Piotr Krawczyk⁵, Piotr Milkiewicz⁶, Huizhang Bao¹, Xiao He¹, Damin Liu¹, Chunhong Fan¹, Abdullah Nasser⁷, Steffi Lopens⁸, Frank Ulrich Weiss⁹, Fabian Frost⁹, Peter Schierack¹⁰, Dirk Roggenbuck¹¹, Yudong Liu¹²

Affiliations

¹ Department of Clinical Laboratory, Peking University People's Hospital, Beijing, China.
² Department of Medicine II, Saarland University Medical Center, Saarland University, Homburg, Germany; Laboratory of Metabolic Liver Diseases, Department of General, Transplant and Liver Surgery, Centre for Preclinical Research, Medical University of Warsaw, Warsaw, Poland.
³ Department of Gastroenterology and Hepatology with Internal Disease Unit, Teaching Hospital No 1 in Rzeszów, Medical Department, University of Rzeszów, Poland.
⁴ Laboratory of Metabolic Liver Diseases, Department of General, Transplant and Liver Surgery, Centre for Preclinical Research, Medical University of Warsaw, Warsaw, Poland.
⁵ Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Poland.
⁶ Liver and Internal Medicine Unit, Department of General, Transplant and Liver Surgery, Medical University of Warsaw, 02-091 Warsaw, Poland; Translational Medicine Group, Pomeranian Medical University, Szczecin, Poland.
⁷ Medipan GmbH, R/D Department, Dahlewitz, Germany.
⁸ Medipan GmbH, R/D Department, Dahlewitz, Germany; Institute of Biotechnology, Faculty Environment and Natural Sciences, Brandenburg University of Technology Cottbus-Senftenberg, Senftenberg, Germany.
⁹ Department of Medicine A, University Medicine Greifswald, Greifswald, Germany.
¹⁰ Institute of Biotechnology, Faculty Environment and Natural Sciences, Brandenburg University of Technology Cottbus-Senftenberg, Senftenberg, Germany; Faculty of Health Sciences Brandenburg, Brandenburg University of Technology Cottbus-Senftenberg, Senftenberg, Germany.
¹¹ Medipan GmbH, R/D Department, Dahlewitz, Germany; Institute of Biotechnology, Faculty Environment and Natural Sciences, Brandenburg University of Technology Cottbus-Senftenberg, Senftenberg, Germany; Faculty of Health Sciences Brandenburg, Brandenburg University of Technology Cottbus-Senftenberg, Senftenberg, Germany.
¹² National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, Beijing 100730, PR China. Electronic address: [email protected].

PMID: 38853092
DOI: 10.1016/j.dld.2024.05.027

Abstract

Background: Anti-glycoprotein 2 (anti-GP2) IgA and antineutrophil-cytoplasmic antibodies to proteinase 3 (PR3-ANCA) have been reported as predictive markers of cholangiocarcinoma (CCA) in patients with primary sclerosing cholangitis (PSC), but their prevalence in CCA patients without PSC remains unclear.

Methods: This study involved Asian discovery (n = 118) and European validation (n = 38) cohorts of CCA patients without PSC, alongside 49 Asian and 82 European pancreatic ductal adenocarcinoma (PDAC) patients, 21 with benign pancreatic neoplasms (BPN) and 45 with hepatocellular carcinoma (HCC), and 157 healthy controls (HC) from Asia and Europe. We analyzed the prevalence of PR3-ANCA, IgA and IgG against GP2₁ and GP2₄, and the CA19-9 levels.

Results: Anti-GP2₁ IgA was the most prevalent in both CCA cohorts (discovery: 55.1 %; validation: 42.1 %) and significantly higher than in other groups except PDAC (all p < 0.05). It demonstrated the best diagnostic performance in distinguishing CCA from disease controls and HC, outperforming tumor markers. No significant correlation was found between anti-GP2₁ IgA levels and CA19-9 levels.

Conclusion: Our findings show that anti-GP2₁ IgA revealing the loss of mucosal tolerance is a potential novel diagnostic biomarker for CCA.

Keywords: Anti-glycoprotein 2; Benign pancreatic neoplasms; Biomarker; Cholangiocarcinoma; Hepatocellular carcinoma; Pancreatic ductal adenocarcinoma.