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Despite recent advances, optimal population-based cancer screening methods remain an unmet need. Due to its early onset, cancer specificity and accessibility in body fluids, aberrant DNA promoter methylation might be a valuable minimally invasive tool for early cancer detection. Herein, we aimed to develop a minimally invasive methylation-based test for simultaneous early detection of LC, PCa and CRC in males, using liquid biopsies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Circulating cell-free DNA was extracted from 102 LC, 121 PCa and 100 CRC patients and 136 asymptomatic donors\u2019 plasma samples. Sodium-bisulfite modification and whole-genome amplification was performed. Promoter methylation levels of<jats:italic>APC<\/jats:italic><jats:sub><jats:italic>me<\/jats:italic><\/jats:sub><jats:italic>, FOXA1<\/jats:italic><jats:sub><jats:italic>me<\/jats:italic><\/jats:sub><jats:italic>, GSTP1<\/jats:italic><jats:sub><jats:italic>me<\/jats:italic><\/jats:sub><jats:italic>, HOXD3<\/jats:italic><jats:sub><jats:italic>me<\/jats:italic><\/jats:sub>,<jats:italic>RAR\u03b22<\/jats:italic><jats:sub><jats:italic>me<\/jats:italic><\/jats:sub><jats:italic>, RASSF1A<\/jats:italic><jats:sub><jats:italic>me<\/jats:italic><\/jats:sub><jats:italic>, SEPT9<\/jats:italic><jats:sub><jats:italic>me<\/jats:italic><\/jats:sub>and<jats:italic>SOX17<\/jats:italic><jats:sub><jats:italic>me<\/jats:italic><\/jats:sub>were assessed by multiplex quantitative methylation-specific PCR.<\/jats:p><jats:p><jats:italic>SEPT9<\/jats:italic><jats:sub><jats:italic>me<\/jats:italic><\/jats:sub>and<jats:italic>SOX17<\/jats:italic><jats:sub><jats:italic>me<\/jats:italic><\/jats:sub>were the only biomarkers shared by all three cancer types, although they detected CRC with limited sensitivity. A \u201cPanCancer\u201d panel (<jats:italic>FOXA1<\/jats:italic><jats:sub><jats:italic>me<\/jats:italic><\/jats:sub><jats:italic>, RAR\u03b22<\/jats:italic><jats:sub><jats:italic>me<\/jats:italic><\/jats:sub>and<jats:italic>RASSF1A<\/jats:italic><jats:sub><jats:italic>me<\/jats:italic><\/jats:sub>) detected LC and PCa with 64% sensitivity and 70% specificity, complemented with \u201cCancerType\u201d panel (<jats:italic>GSTP1<\/jats:italic><jats:sub><jats:italic>me<\/jats:italic><\/jats:sub>and<jats:italic>SOX17<\/jats:italic><jats:sub><jats:italic>me<\/jats:italic><\/jats:sub>) which discriminated between LC and PCa with 93% specificity, but with modest sensitivity. Moreover, a<jats:italic>HOXD3<\/jats:italic><jats:sub><jats:italic>me<\/jats:italic><\/jats:sub>and<jats:italic>RASSF1A<\/jats:italic><jats:sub><jats:italic>me<\/jats:italic><\/jats:sub>panel discriminated small cell lung carcinoma from non-small cell lung carcinoma with 75% sensitivity, 88% specificity, 6.5 LR+ and 0.28 LR\u2013. An<jats:italic>APC<\/jats:italic><jats:sub><jats:italic>me<\/jats:italic><\/jats:sub>and<jats:italic>RASSF1A<\/jats:italic><jats:sub><jats:italic>me<\/jats:italic><\/jats:sub>panel independently predicted disease-specific mortality in LC patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We concluded that a DNA methylation-based test in liquid biopsies might enable minimally invasive screening of LC and PCa, improving patient compliance and reducing healthcare costs. Moreover, it might assist in LC subtyping and prognostication.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s13148-019-0779-x","type":"journal-article","created":{"date-parts":[[2019,12,2]],"date-time":"2019-12-02T15:09:09Z","timestamp":1575299349000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":60,"title":["Early detection of the major male cancer types in blood-based liquid biopsies using a DNA methylation panel"],"prefix":"10.1186","volume":"11","author":[{"given":"Vera","family":"Const\u00e2ncio","sequence":"first","affiliation":[]},{"given":"Sandra P.","family":"Nunes","sequence":"additional","affiliation":[]},{"given":"Catarina","family":"Moreira-Barbosa","sequence":"additional","affiliation":[]},{"given":"Rui","family":"Freitas","sequence":"additional","affiliation":[]},{"given":"Jorge","family":"Oliveira","sequence":"additional","affiliation":[]},{"given":"In\u00eas","family":"Pousa","sequence":"additional","affiliation":[]},{"given":"J\u00falio","family":"Oliveira","sequence":"additional","affiliation":[]},{"given":"Marta","family":"Soares","sequence":"additional","affiliation":[]},{"given":"Carlos Gon\u00e7alves","family":"Dias","sequence":"additional","affiliation":[]},{"given":"Teresa","family":"Dias","sequence":"additional","affiliation":[]},{"given":"Lu\u00eds","family":"Antunes","sequence":"additional","affiliation":[]},{"given":"Rui","family":"Henrique","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4186-5345","authenticated-orcid":false,"given":"Carmen","family":"Jer\u00f3nimo","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2019,12,2]]},"reference":[{"key":"779_CR1","doi-asserted-by":"crossref","unstructured":"Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. 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