{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T13:40:52Z","timestamp":1771076452170,"version":"3.50.1"},"reference-count":42,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,4,7]],"date-time":"2020-04-07T00:00:00Z","timestamp":1586217600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"EOGE, Oncological Fund, Greece","award":["Project 2016-2019"],"award-info":[{"award-number":["Project 2016-2019"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Deregulation of the transcribed ultra-conserved regions (T-UCRs) Uc160, Uc283, and Uc346 has been reported in colorectal cancer (CRC) recently. Here, we investigated promoter methylation of these T-UCRs during the adenoma\u2013carcinoma sequence and their clinical significance in CRC patients. Methylation levels were assessed in CRC, adenomas, infiltrated lymph nodes, and metastatic tissue specimens. In situ hybridization was performed in representative tissue specimens. T-UCRs expression levels were also evaluated in HT-29 colon cancer cells before and after the acquired resistance to 5-fluorouracil (5-FU) and oxaliplatin. A gradual increase in T-UCRs methylation levels from hyperplastic polyps to adenomas and to in situ carcinomas (ISC) and a gradual decrease from ISC to infiltrative and metastatic carcinomas was observed (p &lt; 0.001 for Uc160 and Uc283, p = 0.018 for Uc346). Uc160 and Uc283 methylation was associated with the grade of dysplasia in adenoma specimens (p = 0.034 and p = 0.019, respectively). Furthermore, higher Uc160 methylation, mainly in stage III and IV patients, was related to improved overall survival (OS) in univariate (p = 0.009; HR, 0.366) and multivariate analysis (p = 0.005; HR, 0.240). Similarly, higher methylation of Uc283 was associated with longer OS (p = 0.030). Finally, T-UCRs expression was significantly reduced in HT-29 cells after resistance to chemotherapy. This study suggests that promoter methylation of Uc160, Uc283, and Uc346 is altered during CRC development and that Uc160 and Uc283 methylation may have prognostic significance for CRC patients.<\/jats:p>","DOI":"10.3390\/cancers12040895","type":"journal-article","created":{"date-parts":[[2020,4,8]],"date-time":"2020-04-08T05:59:47Z","timestamp":1586325587000},"page":"895","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Differentially Methylated Ultra-Conserved Regions Uc160 and Uc283 in Adenomas and Adenocarcinomas Are Associated with Overall Survival of Colorectal Cancer Patients"],"prefix":"10.3390","volume":"12","author":[{"given":"Anastasia E.","family":"Kottorou","sequence":"first","affiliation":[{"name":"Clinical and Molecular Oncology Laboratory, Division of Oncology, Medical School, University of Patras, 26504 Rio, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2402-2549","authenticated-orcid":false,"given":"Foteinos-Ioannis D.","family":"Dimitrakopoulos","sequence":"additional","affiliation":[{"name":"Clinical and Molecular Oncology Laboratory, Division of Oncology, Medical School, University of Patras, 26504 Rio, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna G.","family":"Antonacopoulou","sequence":"additional","affiliation":[{"name":"Clinical and Molecular Oncology Laboratory, Division of Oncology, Medical School, University of Patras, 26504 Rio, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georgia","family":"Diamantopoulou","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, University Hospital of Patras, 26504 Rio, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dimitrios","family":"Tsoumas","sequence":"additional","affiliation":[{"name":"Clinical and Molecular Oncology Laboratory, Division of Oncology, Medical School, University of Patras, 26504 Rio, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angelos","family":"Koutras","sequence":"additional","affiliation":[{"name":"Clinical and Molecular Oncology Laboratory, Division of Oncology, Medical School, University of Patras, 26504 Rio, Greece"},{"name":"Division of Oncology, Department of Internal Medicine, University Hospital of Patras, 26504 Rio, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Makatsoris","sequence":"additional","affiliation":[{"name":"Clinical and Molecular Oncology Laboratory, Division of Oncology, Medical School, University of Patras, 26504 Rio, Greece"},{"name":"Division of Oncology, Department of Internal Medicine, University Hospital of Patras, 26504 Rio, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michalis","family":"Stavropoulos","sequence":"additional","affiliation":[{"name":"Department of Surgery, Medical School, University of Patras, 26504 Rio, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Konstantinos C.","family":"Thomopoulos","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, University Hospital of Patras, 26504 Rio, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alicia","family":"Hulbert","sequence":"additional","affiliation":[{"name":"Cancer Center, University of Illinois at Chicago School of Medicine, Chicago, IL 60612, USA"},{"name":"Department of Surgery, University of Illinois at Chicago School of Medicine, Chicago, IL 60612, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vassiliki","family":"Tzelepi","sequence":"additional","affiliation":[{"name":"Department of Pathology, Medical School, University of Patras, 26504 Rio, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haralabos P.","family":"Kalofonos","sequence":"additional","affiliation":[{"name":"Clinical and Molecular Oncology Laboratory, Division of Oncology, Medical School, University of Patras, 26504 Rio, Greece"},{"name":"Division of Oncology, Department of Internal Medicine, University Hospital of Patras, 26504 Rio, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21442","article-title":"Cancer statistics, 2018","volume":"68","author":"Siegel","year":"2018","journal-title":"CA Cancer J. 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