{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:51:04Z","timestamp":1785433864026,"version":"3.56.0"},"reference-count":37,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100022217","name":"Flinders Foundation","doi-asserted-by":"crossref","award":["FFHSG2022"],"award-info":[{"award-number":["FFHSG2022"]}],"id":[{"id":"10.13039\/501100022217","id-type":"DOI","asserted-by":"crossref"}]},{"award":["FFHSG2022"],"award-info":[{"award-number":["FFHSG2022"]}],"id":[{"id":"https:\/\/ror.org\/045thxk12","id-type":"ROR","asserted-by":"publisher"}]},{"name":"DW Henderson AOM Bequest"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Poor outcomes in liver cancer are often driven by late-stage diagnoses and high recurrence rates following surgical resection, highlighting a critical clinical need for non-invasive surveillance tools. This proof-of-concept study investigates the utility of circulating extracellular vesicles (EVs) to track dynamic molecular shifts and monitor patient response following tumour resection. Methods: Small ribonucleic acid (RNA) sequencing was conducted on matched tumour tissue, tissue-derived EVs, and plasma EVs collected at the time of surgery from patients with liver cancer. To capture longitudinal transcriptomic changes, plasma EVs were also collected at a post-operative follow-up appointment. Results: At the time of surgery, the transcriptomic profile of circulating plasma EVs strongly correlated with both the matched tumour tissue and tissue-derived EVs, exhibiting substantial transcript overlap. However, at post-operative follow-up, the circulating EV cargo significantly diverged from the primary tumour profile. This loss of similarity was characterised by a distinct shift in RNA cargo, including 173 uniquely detected transcripts absent at baseline. Conclusions: Circulating EVs accurately reflect the local hepatic transcriptome at the time of surgery, but their profile dynamically and fundamentally diverges once the tumour is removed. This post-surgical divergence provides an initial proof-of-concept that utilising patients as their own internal control to longitudinally profile EV cargo may track the clearance of tumour signals and monitor post-surgical systemic changes, highlighting their potential utility for future longitudinal studies aimed at tracking cancer progression and recurrence.<\/jats:p>","DOI":"10.3390\/cancers18132109","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T15:27:37Z","timestamp":1782746857000},"page":"2109","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Circulating Extracellular Vesicles Reflect Dynamic Shifts in Liver Transcriptome Following Tumour Resection"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3303-1666","authenticated-orcid":false,"given":"Lauren A.","family":"Newman","sequence":"first","affiliation":[{"name":"Flinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Adelaide, SA 5042, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9466-4355","authenticated-orcid":false,"given":"Daniel","family":"Daly","sequence":"additional","affiliation":[{"name":"HPB and Liver Transplant Unit, Flinders Medical Centre, Bedford Park, SA 5042, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0791-6850","authenticated-orcid":false,"given":"Fiona","family":"Whelan","sequence":"additional","affiliation":[{"name":"Department of Molecular and Biomedical Science, University of Adelaide, Adelaide, SA 5005, Australia"},{"name":"Adelaide Microscopy, University of Adelaide, Adelaide, SA 5005, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janina","family":"Kaczmarczyk","sequence":"additional","affiliation":[{"name":"HPB and Liver Transplant Unit, Flinders Medical Centre, Bedford Park, SA 5042, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eu Ling","family":"Neo","sequence":"additional","affiliation":[{"name":"HPB and Liver Transplant Unit, Flinders Medical Centre, Bedford Park, SA 5042, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John W.","family":"Chen","sequence":"additional","affiliation":[{"name":"Flinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Adelaide, SA 5042, Australia"},{"name":"HPB and Liver Transplant Unit, Flinders Medical Centre, Bedford Park, SA 5042, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark E.","family":"Brooke-Smith","sequence":"additional","affiliation":[{"name":"Flinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Adelaide, SA 5042, Australia"},{"name":"HPB and Liver Transplant Unit, Flinders Medical Centre, Bedford Park, SA 5042, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8946-3954","authenticated-orcid":false,"given":"Andrew","family":"Rowland","sequence":"additional","affiliation":[{"name":"Flinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Adelaide, SA 5042, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8976-4714","authenticated-orcid":false,"given":"Sonja","family":"Klebe","sequence":"additional","affiliation":[{"name":"Flinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Adelaide, SA 5042, Australia"},{"name":"Department of Surgical Pathology, SA Pathology at Flinders Medical Centre, Adelaide, SA 5042, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4999-5657","authenticated-orcid":false,"given":"Savio George","family":"Barreto","sequence":"additional","affiliation":[{"name":"Flinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Adelaide, SA 5042, Australia"},{"name":"HPB and Liver Transplant Unit, Flinders Medical Centre, Bedford Park, SA 5042, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4566-5036","authenticated-orcid":false,"given":"Zivile","family":"Useckaite","sequence":"additional","affiliation":[{"name":"Flinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Adelaide, SA 5042, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1598","DOI":"10.1016\/j.jhep.2022.08.021","article-title":"Global burden of primary liver cancer in 2020 and predictions to 2040","volume":"77","author":"Rumgay","year":"2022","journal-title":"J. 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