Exosomal glypican-1 is elevated in pancreatic cancer precursors and can signal genetic predisposition in the absence of endoscopic ultrasound abnormalities.

Autor:	Moutinho-Ribeiro P; Serviço de Gastrenterologia, Centro Hospitalar Universitário de São João, Porto 4200, Portugal.; Faculty of Medicine, University of Porto, Porto 4200, Portugal., Batista IA; Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Porto 4200, Portugal.; IPATIMUP-Institute of Molecular Pathology and Immunology, University of Porto, Porto 4200, Portugal.; Instituto de Ciências Biomédicas Abel Salazar (ICBAS), University of Porto, Porto 4050, Portugal., Quintas ST; Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Porto 4200, Portugal.; IPATIMUP-Institute of Molecular Pathology and Immunology, University of Porto, Porto 4200, Portugal., Adem B; Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Porto 4200, Portugal.; Instituto de Ciências Biomédicas Abel Salazar (ICBAS), University of Porto, Porto 4050, Portugal., Silva M; Serviço de Gastrenterologia, Centro Hospitalar Universitário de São João, Porto 4200, Portugal.; Faculty of Medicine, University of Porto, Porto 4200, Portugal., Morais R; Serviço de Gastrenterologia, Centro Hospitalar Universitário de São João, Porto 4200, Portugal.; Faculty of Medicine, University of Porto, Porto 4200, Portugal., Peixoto A; Serviço de Gastrenterologia, Centro Hospitalar Universitário de São João, Porto 4200, Portugal.; Faculty of Medicine, University of Porto, Porto 4200, Portugal., Coelho R; Serviço de Gastrenterologia, Centro Hospitalar Universitário de São João, Porto 4200, Portugal.; Faculty of Medicine, University of Porto, Porto 4200, Portugal., Costa-Moreira P; Serviço de Gastrenterologia, Centro Hospitalar Universitário de São João, Porto 4200, Portugal.; Faculty of Medicine, University of Porto, Porto 4200, Portugal., Medas R; Serviço de Gastrenterologia, Centro Hospitalar Universitário de São João, Porto 4200, Portugal.; Faculty of Medicine, University of Porto, Porto 4200, Portugal., Lopes S; Serviço de Gastrenterologia, Centro Hospitalar Universitário de São João, Porto 4200, Portugal.; Faculty of Medicine, University of Porto, Porto 4200, Portugal., Vilas-Boas F; Serviço de Gastrenterologia, Centro Hospitalar Universitário de São João, Porto 4200, Portugal.; Faculty of Medicine, University of Porto, Porto 4200, Portugal., Baptista M; Serviço de Cirurgia Geral, Centro Hospitalar Universitário de São João, Porto 4200, Portugal., Dias-Silva D; Unidade de Saúde Familiar Serpa Pinto, ACeS Porto Ocidental, Porto 4250, Portugal., Esteves AL; Unidade de Saúde Familiar Serpa Pinto, ACeS Porto Ocidental, Porto 4250, Portugal., Martins F; Unidade de Saúde Familiar Serpa Pinto, ACeS Porto Ocidental, Porto 4250, Portugal., Lopes J; Serviço de Anatomia Patológica, Centro Hospitalar Universitário de São João, Porto 4200, Portugal., Barroca H; Serviço de Anatomia Patológica, Centro Hospitalar Universitário de São João, Porto 4200, Portugal., Carneiro F; Faculty of Medicine, University of Porto, Porto 4200, Portugal.; Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Porto 4200, Portugal.; IPATIMUP-Institute of Molecular Pathology and Immunology, University of Porto, Porto 4200, Portugal.; Serviço de Anatomia Patológica, Centro Hospitalar Universitário de São João, Porto 4200, Portugal., Macedo G; Serviço de Gastrenterologia, Centro Hospitalar Universitário de São João, Porto 4200, Portugal.; Faculty of Medicine, University of Porto, Porto 4200, Portugal., Melo SA; Faculty of Medicine, University of Porto, Porto 4200, Portugal.; Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Porto 4200, Portugal.; IPATIMUP-Institute of Molecular Pathology and Immunology, University of Porto, Porto 4200, Portugal. smelo@i3s.up.pt.
Jazyk:	angličtina
Zdroj:	World journal of gastroenterology [World J Gastroenterol] 2022 Aug 21; Vol. 28 (31), pp. 4310-4327.
DOI:	10.3748/wjg.v28.i31.4310
Abstrakt:	Background: Individuals within specific risk groups for pancreatic ductal adenocarcinoma (PDAC) [mucinous cystic lesions (MCLs), hereditary risk (HR), and new-late onset diabetes mellitus (NLOD)] represent an opportunity for early cancer detection. Endoscopic ultrasound (EUS) is a premium image modality for PDAC screening and precursor lesion characterization. While no specific biomarker is currently clinically available for this purpose, glypican-1 (GPC1) is overexpressed in the circulating exosomes (crExos) of patients with PDAC compared with healthy subjects or those harboring benign pancreatic diseases. Aim: To evaluate the capacity of GPC1 + crExos to identify individuals at higher risk within these specific groups, all characterized by EUS. Methods: This cross-sectional study with a prospective unicentric cohort included 88 subjects: 40 patients with MCL, 20 individuals with HR, and 20 patients with NLOD. A control group (CG) was submitted to EUS for other reasons than pancreatic pathology, with normal pancreas and absence of hereditary risk factors ( n = 8). The inclusion period was between October 2016 and January 2019, and the study was approved by the Ethics Committee of Centro Hospitalar Universitário de São João, Porto, Portugal. All patients provided written informed consent. EUS and blood tests for quantification of GPC1 + crExos by flow cytometry and carbohydrate antigen 19-9 (CA 19-9) levels by ELISA were performed in all subjects. EUS-guided tissue acquisition was done whenever necessary. For statistical analysis, SPSS ® 27.0 (IBM Corp., Armonk, NY, United States) version was used. All graphs were created using GraphPad Prism 7.00 (GraphPad Software, San Diego, CA, United States). Results: Half of MCLs harbored worrisome features (WF) or high-risk stigmata (HRS). Pancreatic abnormalities were detected by EUS in 10.0% and 35.0% in HR and NLOD individuals, respectively, all considered non-malignant and "harmless." Median levels of GPC1 + crExos were statistically different: MCL [99.4%, interquartile range (IQR): 94.9%-99.8%], HR (82.0%, IQR: 28.9%-98.2%), NLOD (12.6%, IQR: 5.2%-63.4%), and CG (16.2%, IQR: 6.6%-20.1%) ( P < 0.0001). Median levels of CA 19-9 were within the normal range in all groups (standard clinical cut-off of 37 U/mL). Within HR, individuals with a positive history of cancer had higher median levels of GPC1 + crExos (97.9%; IQR: 61.7%-99.5%), compared to those without (59.7%; IQR: 26.3%-96.4%), despite no statistical significance ( P = 0.21). Pancreatic cysts with WF/HRS were statistically associated with higher median levels of GPC1 + crExos (99.6%; IQR: 97.6%-99.8%) compared to those without (96.5%; IQR: 81.3%-99.5%) ( P = 0.011), presenting an area under the receiver operating characteristic curve value of 0.723 (sensitivity 75.0% and specificity 67.7%, using a cut-off of 98.5%; P = 0.012). Conclusion: GPC1 + crExos may act as biomarker to support the diagnosis and stratification of PDAC precursor lesions, and in signaling individuals with genetic predisposition in the absence of EUS abnormalities. Competing Interests: Conflict-of-interest statement: Sónia A Melo holds patents in the field of exosomes biology and are licensed to Codiak Biosciences, Inc. All other authors have no conflicts of interest to declare. (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)
Databáze:	MEDLINE
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