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This study integrated genome-wide DNA methylation profiles and comorbidity patterns to identify the common biomarkers with multi-functional analytics across the aforementioned five cancer types. In addition, gene ontology was used to categorize the biomarkers into several functional groups and establish the relationships between gene functions and cancers. ALX3, HOXD8, IRX1, HOXA9, HRH1, PTPRN2, TRIM58, and NPTX2 were identified as important methylation biomarkers for the five cancers characterized by low five-year survival rates. To extend the applicability of these biomarkers, their annotated genetic functions were explored through GO and KEGG pathway analyses. The combination of ALX3, NPTX2, and TRIM58 was selected from distinct functional groups. An accuracy prediction of 93.3% could be achieved by validating the ten most common cancers, including the initial five low-survival-rate cancer types.<\/jats:p>","DOI":"10.3389\/fbinf.2025.1523524","type":"journal-article","created":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T06:41:59Z","timestamp":1738046519000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["DNA methylation biomarker analysis from low-survival-rate cancers based on genetic functional approaches"],"prefix":"10.3389","volume":"5","author":[{"given":"Yi-Hsuan","family":"Tsai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prasenjit","family":"Mitra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Taniar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tun-Wen","family":"Pai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,1,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1016\/j.websem.2003.12.003","article-title":"A short study on the success of the Gene Ontology","volume":"1","author":"Bada","year":"2004","journal-title":"J. web Semant."},{"key":"B2","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1053\/j.gastro.2009.09.059","article-title":"History of peptic ulcer disease and pancreatic cancer risk in men","volume":"138","author":"Bao","year":"2010","journal-title":"Gastroenterology"},{"key":"B3","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1016\/j.path.2016.05.007","article-title":"Benign tumors and tumorlike lesions of the pancreas","volume":"9","author":"Basturk","year":"2016","journal-title":"Surg. 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