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This leads to delayed diagnosis and reduced treatment efficiency. Therefore, novel and effective CRC markers are needed. In this study, we conducted circRNA expression profiling on GSE datasets and identified <jats:italic>circ-CCDC66<\/jats:italic> as a potential marker. Through qPCR analysis of plasma samples from 50 CRC patients, 50 with colorectal polyps, and 50 healthy individuals, <jats:italic>circ-CCDC66<\/jats:italic> emerged as a promising biomarker for CRC detection capable of identifying polyps among healthy individuals. Furthermore, plasma <jats:italic>circ-CCDC66<\/jats:italic> levels exhibited superior diagnostic accuracy, with an AUC of 0.920, compared to traditional markers, such as serum CEA and CA19-9. Remarkably, the combined detection of circ-CCDC66, CEA, and CA19-9 further increased the AUC for distinguishing the colorectal polyps\u2019 group from the healthy control group to 0.991, with sensitivity and specificity increasing to 98% and 96%, respectively. Additionally, a <jats:italic>circ-CCDC66<\/jats:italic>-miRNA-mRNA regulatory network was established to provide insight into how circ-CCDC66 influences CRC pathways. This pioneering study highlights circ-CCDC66\u2019s clinical relevance as a blood-based diagnostic marker for CRC and offers valuable insights into future developments in the diagnosis and treatment of the disease.<\/jats:p>","DOI":"10.1038\/s41598-025-95685-5","type":"journal-article","created":{"date-parts":[[2025,4,4]],"date-time":"2025-04-04T22:17:49Z","timestamp":1743805069000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Exploring the diagnostic potential of plasma circ-CCDC66 in colorectal cancer"],"prefix":"10.1038","volume":"15","author":[{"given":"Zhuoting","family":"Han","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lok Ting","family":"Chu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaocong","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,3]]},"reference":[{"key":"95685_CR1","doi-asserted-by":"crossref","unstructured":"Hamdy, N. 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Informed consent was obtained from all individual participants included in the study. All blood samples for experiment were collected with the approval from Ethics Committee of The Second Affiliated Hospital of Guangdong Medical University (Ethics Approval Number: PJKT2023-002).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}],"article-number":"11463"}}