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

作     者：Pedro Moutinho-Ribeiro Ines A Batista Sofia T Quintas Bárbara Adem Marco Silva Rui Morais Armando Peixoto Rosa Coelho Pedro Costa-Moreira Renato Medas Susana Lopes Filipe Vilas-Boas Manuela Baptista Diogo Dias-Silva Ana L Esteves Filipa Martins Joanne Lopes Helena Barroca Fátima Carneiro Guilherme Macedo Sonia A Melo 

作者机构：Serviço de GastrenterologiaCentro Hospitalar Universitário de Sao JoaoPorto 4200Portugal Faculty of MedicineUniversity of PortoPorto 4200Portugal Instituto de Investigacao e Inovacao em Saúde(i3S)Universidade do PortoPorto 4200Portugal IPATIMUP-Institute of Molecular Pathology and ImmunologyUniversity of PortoPorto 4200Portugal Instituto de Ciencias Biomédicas Abel Salazar(ICBAS)University of PortoPorto 4050Portugal Servico de Cirurgia GeralCentro Hospitalar Universitário de Sao JoaoPorto 4200Portugal Unidade de Saúde Familiar Serpa PintoACeS Porto OcidentalPorto 4250Portugal Serviço de Anatomia PatológicaCentro Hospitalar Universitário de Sao JoaoPorto 4200Portugal 

出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)

年 卷 期：2022年第28卷第31期

页      面：4310-4327页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：Supported by Guilherme Macedo team was supported by the Portuguese Society of Digestive Endoscopy(SPED)2017 Research Grant,No.SG/CHSJ-A2017 Norte Portugal Regional Programme(NORTE 2020)under the PORTUGAL 2020 Partnership Agreement through the European Regional Development Fund(ERDF)to Sonia A Melo,No.NORTE-01-0145-FEDER-000029 National Funds through Foundation for Science and Technology(FCT)to Sonia A Melo,No.POCI-01-0145-FEDER-32189 Foundation for Science and Technology(FCT)to Bárbara Adem and Ines A Batista,No.PD/BD/135546/2018 and No.SFRH/BD/144854/2019 

主　　题：Glypican-1 Circulating exosomes Endoscopic ultrasound Pancreatic cancer risk groups Pancreatic cancer precursor lesions Genetic predisposition 

摘      要：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 *** ultrasound(EUS)is a premium image modality for PDAC screening and precursor lesion *** 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 *** To evaluate the capacity of GPC1+crExos to identify individuals at higher risk within these specific groups,all characterized by *** 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,*** patients provided written informed *** 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 ***-guided tissue acquisition was done whenever *** statistical analysis,SPSS®27.0(IBM Corp.,Armonk,NY,United States)version was *** 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(8