1. Loss of mucosal tolerance to glycoprotein 2 isoform 1 is a potential novel diagnostic biomarker for cholangiocarcinoma.
- Author
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Xia CS, Krawczyk M, Di C, Krupa Ł, Kruk B, Krawczyk P, Milkiewicz P, Bao H, He X, Liu D, Fan C, Nasser A, Lopens S, Weiss FU, Frost F, Schierack P, Roggenbuck D, and Liu Y
- Subjects
- Humans, Male, Female, Middle Aged, Aged, Case-Control Studies, Adult, Europe, Asia, Immunoglobulin A blood, Carcinoma, Hepatocellular diagnosis, Carcinoma, Hepatocellular immunology, Pancreatic Neoplasms diagnosis, Pancreatic Neoplasms immunology, Liver Neoplasms diagnosis, Liver Neoplasms immunology, Carcinoma, Pancreatic Ductal diagnosis, Carcinoma, Pancreatic Ductal immunology, Carcinoma, Pancreatic Ductal blood, GPI-Linked Proteins, Cholangiocarcinoma diagnosis, Cholangiocarcinoma immunology, Bile Duct Neoplasms diagnosis, Biomarkers, Tumor blood
- 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 GP2
1 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., Competing Interests: Declaration of competing interest Dirk Roggenbuck has ownership of Medipan and GA Generic Assays corporation stocks and profits earned from the stocks. The other authors declare that they have no conflicts of interest., (Copyright © 2024 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)- Published
- 2025
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