{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:26:00Z","timestamp":1760149560644,"version":"build-2065373602"},"reference-count":53,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2023,8,20]],"date-time":"2023-08-20T00:00:00Z","timestamp":1692489600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Locally advanced rectal cancer (LARC) has traditionally been treated with trimodality therapy consisting of neoadjuvant radiation +\/\u2212 chemotherapy, surgery, and adjuvant chemotherapy. There is currently a clinical need for biomarkers to predict treatment response and outcomes, especially during neoadjuvant therapy. Liquid biopsies in the form of circulating tumour cells (CTCs) and circulating nucleic acids in particular microRNAs (miRNA) are novel, the latter also being highly stable and clinically relevant regulators of disease. We studied a prospective cohort of 52 patients with LARC, and obtained samples at baseline, during treatment, and post-treatment. We enumerated CTCs during chemoradiation at these three time-points, using the IsofluxTM (Fluxion Biosciences Inc., Alameda, CA, USA) CTC Isolation and detection platform. We then subjected the isolated CTCs to miRNA expression analyses, using a panel of 106 miRNA candidates. We identified CTCs in 73% of patients at baseline; numbers fell and miRNA expression profiles also changed during treatment. Between baseline and during treatment (week 3) time-points, three microRNAs (hsa-miR-95, hsa-miR-10a, and hsa-miR-16-1*) were highly differentially expressed. Importantly, hsa-miR-19b-3p and hsa-miR-483-5p were found to correlate with good response to treatment. The latter (hsa-miR-483-5p) was also found to be differentially expressed between good responders and poor responders. These miRNAs represent potential predictive biomarkers, and thus a potential miRNA-based treatment strategy. In this study, we demonstrate that CTCs are present and can be isolated in the non-metastatic early-stage cancer setting, and their associated miRNA profiles can potentially be utilized to predict treatment response.<\/jats:p>","DOI":"10.3390\/cancers15164184","type":"journal-article","created":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T01:46:56Z","timestamp":1692582416000},"page":"4184","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Circulating Tumour Cell Associated MicroRNA Profiles Change during Chemoradiation and Are Predictive of Response in Locally Advanced Rectal Cancer"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5940-7137","authenticated-orcid":false,"given":"Stephanie H.","family":"Lim","sequence":"first","affiliation":[{"name":"Medical Oncology Group, Ingham Institute for Applied Medical Research, Liverpool, NSW 2170, Australia"},{"name":"Department of Medical Oncology, Macarthur Cancer Therapy Centre, Campbelltown, NSW 2560, Australia"},{"name":"Liverpool Clinical School, Western Sydney University, Liverpool, NSW 2170, Australia"}]},{"given":"Wei","family":"Chua","sequence":"additional","affiliation":[{"name":"Medical Oncology Group, Ingham Institute for Applied Medical Research, Liverpool, NSW 2170, Australia"},{"name":"Liverpool Clinical School, Western Sydney University, Liverpool, NSW 2170, Australia"},{"name":"Department of Medical Oncology, Liverpool Hospital, Liverpool, NSW 2170, Australia"}]},{"given":"Weng","family":"Ng","sequence":"additional","affiliation":[{"name":"Medical Oncology Group, Ingham Institute for Applied Medical Research, Liverpool, NSW 2170, Australia"},{"name":"Liverpool Clinical School, Western Sydney University, Liverpool, NSW 2170, Australia"},{"name":"Department of Medical Oncology, Liverpool Hospital, Liverpool, NSW 2170, Australia"}]},{"given":"Emilia","family":"Ip","sequence":"additional","affiliation":[{"name":"Medical Oncology Group, Ingham Institute for Applied Medical Research, Liverpool, NSW 2170, Australia"},{"name":"Liverpool Clinical School, Western Sydney University, Liverpool, NSW 2170, Australia"},{"name":"Department of Medical Oncology, Liverpool Hospital, Liverpool, NSW 2170, Australia"}]},{"given":"Tania M.","family":"Marques","sequence":"additional","affiliation":[{"name":"BioISI\u2014Biosystems & Integrative Sciences Institute, Faculty of Sciences, University of Lisbon, 1749-016 Lisbon, Portugal"}]},{"given":"Nham T.","family":"Tran","sequence":"additional","affiliation":[{"name":"School Biomedical Engineering, Faculty of Engineering and IT, University of Technology Sydney, Ultimo, NSW 2007, Australia"}]},{"given":"Margarida","family":"Gama-Carvalho","sequence":"additional","affiliation":[{"name":"BioISI\u2014Biosystems & Integrative Sciences Institute, Faculty of Sciences, University of Lisbon, 1749-016 Lisbon, Portugal"}]},{"given":"Ray","family":"Asghari","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Bankstown Hospital, Bankstown, NSW 2200, Australia"}]},{"given":"Christopher","family":"Henderson","sequence":"additional","affiliation":[{"name":"NSW Health Pathology, Liverpool Hospital, Liverpool, NSW 2170, Australia"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0522-8771","authenticated-orcid":false,"given":"Yafeng","family":"Ma","sequence":"additional","affiliation":[{"name":"Medical Oncology Group, Ingham Institute for Applied Medical Research, Liverpool, NSW 2170, Australia"}]},{"given":"Paul","family":"de Souza","sequence":"additional","affiliation":[{"name":"Medical Oncology Group, Ingham Institute for Applied Medical Research, Liverpool, NSW 2170, Australia"},{"name":"Liverpool Clinical School, Western Sydney University, Liverpool, NSW 2170, Australia"},{"name":"School of Medicine, University of Wollongong, Wollongong, NSW 2522, Australia"},{"name":"South West Sydney Clinical School, University of New South Wales, Liverpool, NSW 2170, Australia"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0601-924X","authenticated-orcid":false,"given":"Kevin J.","family":"Spring","sequence":"additional","affiliation":[{"name":"Medical Oncology Group, Ingham Institute for Applied Medical Research, Liverpool, NSW 2170, Australia"},{"name":"Liverpool Clinical School, Western Sydney University, Liverpool, NSW 2170, Australia"},{"name":"South West Sydney Clinical School, University of New South Wales, Liverpool, NSW 2170, Australia"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1926","DOI":"10.1200\/JCO.2011.40.1836","article-title":"Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: Results of the German CAO\/ARO\/AIO-94 randomized phase III trial after a median follow-up of 11 years","volume":"30","author":"Sauer","year":"2012","journal-title":"J. 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