{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:06:33Z","timestamp":1791288393419,"version":"4.3.0"},"reference-count":102,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T00:00:00Z","timestamp":1744329600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"POR \u201cMalattie Rare\u201d","award":["521"],"award-info":[{"award-number":["521"]}]},{"name":"POR \u201cMalattie Rare\u201d","award":["CUP B63C25000300002"],"award-info":[{"award-number":["CUP B63C25000300002"]}]},{"name":"Regione Campania, Realizzazione di progetti di ricerca, sviluppo e innovazione nel campo delle malattie rare","award":["521"],"award-info":[{"award-number":["521"]}]},{"name":"Regione Campania, Realizzazione di progetti di ricerca, sviluppo e innovazione nel campo delle malattie rare","award":["CUP B63C25000300002"],"award-info":[{"award-number":["CUP B63C25000300002"]}]},{"name":"LUNG INNOVA DIAGNOSTIC","award":["521"],"award-info":[{"award-number":["521"]}]},{"name":"LUNG INNOVA DIAGNOSTIC","award":["CUP B63C25000300002"],"award-info":[{"award-number":["CUP B63C25000300002"]}]},{"name":"dall\u2019ente finanziatore","award":["521"],"award-info":[{"award-number":["521"]}]},{"name":"dall\u2019ente finanziatore","award":["CUP B63C25000300002"],"award-info":[{"award-number":["CUP B63C25000300002"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Neuroendocrine neoplasms (NENs) comprise a heterogeneous tumor group arising from neuroendocrine cells, commonly originating in the gastroenteropancreatic tract and bronchopulmonary system. Their incidence has risen significantly, owing to improved diagnostic techniques and increased clinical recognition. While previous reviews have explored the molecular and genetic basis of NENs, limited attention has been given to the role of epigenetic modifications, particularly DNA methylation, in tumorigenesis and disease progression. This review focuses on lung, pancreas, and thyroid well-differentiated neuroendocrine tumors (NETs), highlighting epigenetic mechanisms, particularly DNA methylation, as promising biomarkers for early diagnosis and risk stratification. Aberrant DNA methylation can silence key tumor suppressor genes, including RASSF1A and CDKN2A, thereby promoting tumorigenesis. Integrating DNA methylation profiles with conventional biomarkers such as chromogranin A (CgA) may enhance diagnostic accuracy and inform therapeutic strategies. Emerging epigenetic therapies offer potential avenues for personalized treatment based on molecular profiling. Unlike prior reviews that broadly cover genetic and epigenetic changes in NENs, this review uniquely emphasizes the translational potential of epigenetic biomarkers in clinical practice. By synthesizing recent findings and evaluating their clinical implications, we aim to bridge the gap between molecular research and practical applications in diagnosis, prognosis, and therapy.<\/jats:p>","DOI":"10.3390\/jcm14082622","type":"journal-article","created":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T05:38:26Z","timestamp":1744349906000},"page":"2622","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Epigenetic Modifications as Novel Biomarkers for Diagnosis, Prognosis, and Therapeutic Targeting in Thyroid, Pancreas, and Lung Neuroendocrine Tumors"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-5630-3956","authenticated-orcid":false,"given":"Federica","family":"Colapietra","sequence":"first","affiliation":[{"name":"Department of Precision Medicine, University of Campania Luigi Vanvitelli, Via Abramo Lincoln, 5, 81100 Caserta, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Della Monica","sequence":"additional","affiliation":[{"name":"Department of Advanced Medical and Surgical Science, University of Campania Luigi Vanvitelli, Via Abramo Lincoln, 5, 81100 Caserta, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaella","family":"Di Napoli","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, University of Campania Luigi Vanvitelli, Via Abramo Lincoln, 5, 81100 Caserta, Italy"},{"name":"Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F\u00e1bio","family":"Fran\u00e7a Vieira e Silva","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, University of Campania Luigi Vanvitelli, Via Abramo Lincoln, 5, 81100 Caserta, Italy"},{"name":"Department of Pathology, Health Research Institute of Santiago de Compostela (FIDIS), Santiago de Compostela University Clinical Hospital, University of Santiago de Compostela, Choupana Street, s\/n, 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuliana","family":"Settembre","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, University of Campania Luigi Vanvitelli, Via Abramo Lincoln, 5, 81100 Caserta, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Michela","family":"Marino","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, University of Campania Luigi Vanvitelli, Via Abramo Lincoln, 5, 81100 Caserta, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8758-1415","authenticated-orcid":false,"given":"Andrea","family":"Ballini","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, University of Campania Luigi Vanvitelli, Via Abramo Lincoln, 5, 81100 Caserta, Italy"},{"name":"Department of Clinical and Experimental Medicine, University of Foggia, Via Napoli, 20, 71122 Foggia, Italy"},{"name":"Department of Life Science, Health and Health Professions, Link Campus University, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9521-2521","authenticated-orcid":false,"given":"Stefania","family":"Cantore","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, University of Campania Luigi Vanvitelli, Via Abramo Lincoln, 5, 81100 Caserta, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Di Domenico","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, University of Campania Luigi Vanvitelli, Via Abramo Lincoln, 5, 81100 Caserta, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"R153","DOI":"10.1530\/ERC-13-0125","article-title":"Incidence of gastroenteropancreatic neuroendocrine tumours: A systematic review of the literature","volume":"21","author":"Fraenkel","year":"2014","journal-title":"Endocr. 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