{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T13:43:04Z","timestamp":1784641384428,"version":"3.55.0"},"reference-count":60,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,9,26]],"date-time":"2022-09-26T00:00:00Z","timestamp":1664150400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Australian Research Training Program (RTP) Scholarship, University of Newcastle, Australia, and the Collaborative Grant from the National Cancer Council of Malaysia","award":["CDF181205"],"award-info":[{"award-number":["CDF181205"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Breast cancer-related lymphedema (BCRL) is a form of secondary lymphedema that is characterized by abnormal swelling of one or both arms due to the accumulation of lymph fluid in the interstitial tissue spaces, resulting from obstruction of the lymphatic vessels due to surgery insults, radiotherapy, or chemotherapy. Due to the multifactorial nature of this condition, the pathogenesis of secondary lymphedema remains unclear and the search for molecular factors associated with the condition is ongoing. This study aimed to identify serum microRNAs and adipokines associated with BCRL. Blood was collected from 113 breast cancer survivors and processed to obtain serum for small RNA-sequencing (BCRL vs. non-BCRL, n = 7 per group). MicroRNAs that were differentially expressed (fold change &gt;1.5, p &lt; 0.05) between lymphedema cases and those without lymphedema were further quantified in a validation cohort through quantitative reverse transcription PCR (BCRL n = 16, non-BCRL, n = 83). Leptin and adiponectin levels were measured in a combined cohort (BCRL n = 23, non-BCRL n = 90) using enzyme-linked immunosorbent assays. Two of the most significantly upregulated microRNAs, miR-199a-3p and miR-151a-3p, were strongly correlated with the onset of lymphedema and diabetes mellitus in the BCRL group. Leptin levels were higher in the BCRL cohort compared to the non-BCRL cohort (p &lt; 0.05). A metabolic syndrome biomarker, the adiponectin\/leptin ratio, was found to be lower in the BCRL group than in the non-BCRL group (median: 0.28 vs. 0.41, p &lt; 0.05). Extensive studies on the mechanisms of the identified microRNAs and association of leptin with arm lymphedema may provide new insights on the potential biomarkers for lymphedema that should be followed up in a prospective cohort study.<\/jats:p>","DOI":"10.3390\/ijms231911359","type":"journal-article","created":{"date-parts":[[2022,9,27]],"date-time":"2022-09-27T23:12:12Z","timestamp":1664320332000},"page":"11359","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Evaluation of Circulating MicroRNAs and Adipokines in Breast Cancer Survivors with Arm Lymphedema"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3047-0671","authenticated-orcid":false,"given":"Khairunnisa\u2019 Md","family":"Yusof","sequence":"first","affiliation":[{"name":"School of Biomedical Sciences and Pharmacy, College of Medicine, Health and Wellbeing, The University of Newcastle, Newcastle, NSW 2308, Australia"},{"name":"Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia"},{"name":"Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9819-5982","authenticated-orcid":false,"given":"Kira","family":"Groen","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences and Pharmacy, College of Medicine, Health and Wellbeing, The University of Newcastle, Newcastle, NSW 2308, Australia"},{"name":"Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rozita","family":"Rosli","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maha","family":"Abdullah","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rozi","family":"Mahmud","sequence":"additional","affiliation":[{"name":"Department of Radiology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2285-9118","authenticated-orcid":false,"given":"Kelly A.","family":"Avery-Kiejda","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences and Pharmacy, College of Medicine, Health and Wellbeing, The University of Newcastle, Newcastle, NSW 2308, Australia"},{"name":"Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1016\/S0140-6736(17)33326-3","article-title":"Global surveillance of trends in cancer survival 2000-14 (CONCORD-3): Analysis of individual records for 37 513 025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries","volume":"391","author":"Allemani","year":"2018","journal-title":"Lancet"},{"key":"ref_2","unstructured":"National Cancer Registry Department, National Cancer Institute (2018). 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