{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T04:41:34Z","timestamp":1781239294930,"version":"3.54.1"},"reference-count":49,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T00:00:00Z","timestamp":1757548800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Prostate cancer (PCa) is the second most common cancer and the fourth leading cause of cancer death in men worldwide. PSA screening for PCa diagnosis is not disease-specific; the discovery of novel and efficient biomarkers is therefore recommended. The concentration and integrity of circulating cell-free DNA (ccfDNA) in the blood of PCa patients could represent innovative and more specific tools for the clinical management of PCa. Digital droplet PCR (ddPCR) was used to determine the copy number ratio of ALU 260\/111 bp and LINE-1 266\/97 bp in the plasma of a cohort of 40 PCa and 18 BPH patients in a blinded prospective study. The amount of ccfDNA in the plasma of PCa and BPH patients was calculated from the EEF1A2 and ESR1 gene copy numbers. The ALU 260\/111 and LINE-1 266\/97 copy number ratios were significantly lower in the plasma of PCa patients compared to benign prostatic hyperplasia (BPH) ones (p-value; ALU 260\/111: 0.006; LINE-1 266\/97: 0.037). The area under the curve (AUC) indicated a good accuracy of two ratios and their product (ALU 260\/111 * LINE 266\/97, A*L) in discriminating PCa patients from BPH ones (AUC; ALU 260\/111: 0.72; LINE-1 266\/97: 0.67; A*L: 0.76). The ccfDNA concentration measured by EEF1A2 and ESR1 targets was significantly higher in the plasma of PCa patients compared to BPH patients, (p-value: EEF1A2, 0.017; ESR1, 0.024). The pilot ddPCR analysis of the ALU 260\/111 and LINE-1 266\/97 ratios in plasma indicates a new, reproducible and specific method for improving the early diagnosis of PCa. Further studies on larger cohorts are needed to confirm the results and clinical application.<\/jats:p>","DOI":"10.3390\/ijms26188862","type":"journal-article","created":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T15:10:46Z","timestamp":1757603446000},"page":"8862","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["LINE-1 266\/97 and ALU 260\/111 Copy Number Ratios in Circulating Cell-Free DNA in Plasma as Potential Biomarkers for the Detection of Prostate Cancer: A Pilot Case-Control Study"],"prefix":"10.3390","volume":"26","author":[{"given":"Domenico","family":"Tierno","sequence":"first","affiliation":[{"name":"Department of Medicine, Surgery and Health Science, University of Trieste, 34129 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7355-7625","authenticated-orcid":false,"given":"Nicola","family":"Pavan","sequence":"additional","affiliation":[{"name":"Department of Surgical, Oncological, and Oral Sciences, University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4160-3479","authenticated-orcid":false,"given":"Fabiola","family":"Giudici","sequence":"additional","affiliation":[{"name":"Cancer Epidemiologic Unit, Centro di Riferimento Oncologico di Aviano (CRO), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), 33081 Aviano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9704-6651","authenticated-orcid":false,"given":"Gabriele","family":"Grassi","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Health Science, University of Trieste, 34129 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Valeri","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, University of Trieste, 34127 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"Zanconati","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Health Science, University of Trieste, 34129 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3272-528X","authenticated-orcid":false,"given":"Fabio","family":"Traunero","sequence":"additional","affiliation":[{"name":"Urological Clinic, Department of Medicine, Surgery and Health Sciences, University of Trieste, 34149 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2431-5296","authenticated-orcid":false,"given":"Giovanni","family":"Liguori","sequence":"additional","affiliation":[{"name":"Urological Clinic, Department of Medicine, Surgery and Health Sciences, University of Trieste, 34149 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8662-138X","authenticated-orcid":false,"given":"Bruna","family":"Scaggiante","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, University of Trieste, 34127 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3029","DOI":"10.1002\/cncr.33587","article-title":"The Ever-Increasing Importance of Cancer as a Leading Cause of Premature Death Worldwide","volume":"127","author":"Bray","year":"2021","journal-title":"Cancer"},{"key":"ref_2","first-page":"10","article-title":"Cancer Statistics, 2025","volume":"75","author":"Siegel","year":"2025","journal-title":"CA Cancer J. 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