{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T02:09:51Z","timestamp":1789610991024,"version":"build-2803163510"},"reference-count":49,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2021,7,15]],"date-time":"2021-07-15T00:00:00Z","timestamp":1626307200000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004622","name":"KWF Kankerbestrijding","doi-asserted-by":"publisher","award":["KWF\u20105510"],"award-info":[{"award-number":["KWF\u20105510"]}],"id":[{"id":"10.13039\/501100004622","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003958","name":"Stichting voor de Technische Wetenschappen","doi-asserted-by":"publisher","award":["CANCER\u2010ID Project"],"award-info":[{"award-number":["CANCER\u2010ID Project"]}],"id":[{"id":"10.13039\/501100003958","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Extracellular Vesicle"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Minimally\u2010invasive tools to assess tumour presence and burden may improve clinical management. FDG\u2010PET (metabolic) imaging is the current gold standard for interim response assessment in patients with classical Hodgkin Lymphoma (cHL), but this technique cannot be repeated frequently. Here we show that microRNAs (miRNA) associated with tumour\u2010secreted extracellular vesicles (EVs) in the circulation of cHL patients may improve response assessment. Small RNA sequencing and qRT\u2010PCR reveal that the relative abundance of cHL\u2010expressed miRNAs, miR\u2010127\u20103p, miR\u2010155\u20105p, miR\u201021\u20105p, miR\u201024\u20103p and let\u20107a\u20105p is up to hundred\u2010fold increased in plasma EVs of cHL patients pre\u2010treatment when compared to complete metabolic responders (CMR). Notably, in partial responders (PR) or treatment\u2010refractory cases (<jats:italic>n\u00a0<\/jats:italic>=\u00a010) the EV\u2010miRNA levels remain elevated. In comparison, tumour specific copy number variations (CNV) were detected in cell\u2010free DNA of 8 out of 10 newly diagnosed cHL patients but not in patients with PR. Combining EV\u2010miR\u2010127\u20103p and\/or EV\u2010let\u20107a\u20105p levels, with serum TARC (a validated protein cHL biomarker), increases the accuracy for predicting PET\u2010status (<jats:italic>n\u00a0<\/jats:italic>=\u00a0129) to an area under the curve of 0.93 (CI: 0.87\u20100.99), 93.5% sensitivity, 83.8\/85.0% specificity and a negative predictive value of 96%. Thus the level of tumour\u2010associated miRNAs in plasma EVs is predictive of metabolic tumour activity in cHL patients. Our findings suggest that plasma EV\u2010miRNA are useful for detection of small residual lesions and may be applied as serial response prediction tool.<\/jats:p>","DOI":"10.1002\/jev2.12121","type":"journal-article","created":{"date-parts":[[2021,7,16]],"date-time":"2021-07-16T01:19:13Z","timestamp":1626398353000},"source":"Crossref","is-referenced-by-count":33,"title":["Extracellular vesicle miRNA predict FDG\u2010PET status in patients with classical Hodgkin Lymphoma"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3551-0038","authenticated-orcid":false,"given":"Esther E. E.","family":"Drees","sequence":"first","affiliation":[{"name":"Department of Pathology Cancer Center Amsterdam Amsterdam UMC Vrije Universiteit Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0220-3496","authenticated-orcid":false,"given":"Margaretha G. M.","family":"Roemer","sequence":"additional","affiliation":[{"name":"Department of Pathology Cancer Center Amsterdam Amsterdam UMC Vrije Universiteit Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nils J.","family":"Groenewegen","sequence":"additional","affiliation":[{"name":"Department of Pathology Cancer Center Amsterdam Amsterdam UMC Vrije Universiteit Amsterdam  Amsterdam The Netherlands"},{"name":"ExBiome B.V.  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3843-494X","authenticated-orcid":false,"given":"Jennifer","family":"Perez\u2010Boza","sequence":"additional","affiliation":[{"name":"Department of Pathology Cancer Center Amsterdam Amsterdam UMC Vrije Universiteit Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monique A. J.","family":"van Eijndhoven","sequence":"additional","affiliation":[{"name":"Department of Pathology Cancer Center Amsterdam Amsterdam UMC Vrije Universiteit Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leah I.","family":"Prins","sequence":"additional","affiliation":[{"name":"Department of Pathology Cancer Center Amsterdam Amsterdam UMC Vrije Universiteit Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra A. W. M.","family":"Verkuijlen","sequence":"additional","affiliation":[{"name":"Department of Pathology Cancer Center Amsterdam Amsterdam UMC Vrije Universiteit Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan\u2010Mai","family":"Tran","sequence":"additional","affiliation":[{"name":"Department of Pathology Cancer Center Amsterdam Amsterdam UMC Vrije Universiteit Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Driessen","sequence":"additional","affiliation":[{"name":"Department of Hematology Amsterdam UMC Cancer Center Amsterdam, University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. J. C.","family":"Zwezerijnen","sequence":"additional","affiliation":[{"name":"Department of Radiology and Nuclear Medicine Cancer Center Amsterdam Amsterdam UMC Vrije Universiteit Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phylicia","family":"Stathi","sequence":"additional","affiliation":[{"name":"Department of Pathology Cancer Center Amsterdam Amsterdam UMC Vrije Universiteit Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Mol","sequence":"additional","affiliation":[{"name":"Department of Pathology Cancer Center Amsterdam Amsterdam UMC Vrije Universiteit Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joey J. J. P.","family":"Karregat","sequence":"additional","affiliation":[{"name":"Department of Pathology Cancer Center Amsterdam Amsterdam UMC Vrije Universiteit Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aikaterini","family":"Kalantidou","sequence":"additional","affiliation":[{"name":"Department of Pathology Cancer Center Amsterdam Amsterdam UMC Vrije Universiteit Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Vall\u00e9s\u2010Mart\u00ed","sequence":"additional","affiliation":[{"name":"Department of Pathology Cancer Center Amsterdam Amsterdam UMC Vrije Universiteit Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. J.","family":"Molenaar","sequence":"additional","affiliation":[{"name":"Department of Pathology Cancer Center Amsterdam Amsterdam UMC Vrije Universiteit Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernesto","family":"Aparicio\u2010Puerta","sequence":"additional","affiliation":[{"name":"Department of Genetics Computational Epigenomics and Bioinformatics University of Granada Granada  Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"van Dijk","sequence":"additional","affiliation":[{"name":"Department of Pathology Cancer Center Amsterdam Amsterdam UMC Vrije Universiteit Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bauke","family":"Ylstra","sequence":"additional","affiliation":[{"name":"Department of Pathology Cancer Center Amsterdam Amsterdam UMC Vrije Universiteit Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catharina G. 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Amsterdam The Netherlands"},{"name":"Department of Genetics Computational Epigenomics and Bioinformatics University of Granada Granada  Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daphne","family":"de Jong","sequence":"additional","affiliation":[{"name":"Department of Pathology Cancer Center Amsterdam Amsterdam UMC Vrije Universiteit Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1074-5922","authenticated-orcid":false,"given":"Jos\u00e9e M.","family":"Zijlstra","sequence":"additional","affiliation":[{"name":"Department of Hematology Cancer Center Amsterdam Amsterdam UMC Vrije Universiteit Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7357-4406","authenticated-orcid":false,"given":"D. 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