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Early detection of the major male cancer types in blood-based liquid biopsies using a DNA methylation panel
BACKGROUND: Lung (LC), prostate (PCa) and colorectal (CRC) cancers are the most incident in males worldwide. 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 prom...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6889617/ https://www.ncbi.nlm.nih.gov/pubmed/31791387 http://dx.doi.org/10.1186/s13148-019-0779-x |
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author | Constâncio, Vera Nunes, Sandra P. Moreira-Barbosa, Catarina Freitas, Rui Oliveira, Jorge Pousa, Inês Oliveira, Júlio Soares, Marta Dias, Carlos Gonçalves Dias, Teresa Antunes, Luís Henrique, Rui Jerónimo, Carmen |
author_facet | Constâncio, Vera Nunes, Sandra P. Moreira-Barbosa, Catarina Freitas, Rui Oliveira, Jorge Pousa, Inês Oliveira, Júlio Soares, Marta Dias, Carlos Gonçalves Dias, Teresa Antunes, Luís Henrique, Rui Jerónimo, Carmen |
author_sort | Constâncio, Vera |
collection | PubMed |
description | BACKGROUND: Lung (LC), prostate (PCa) and colorectal (CRC) cancers are the most incident in males worldwide. 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. RESULTS: Circulating cell-free DNA was extracted from 102 LC, 121 PCa and 100 CRC patients and 136 asymptomatic donors’ plasma samples. Sodium-bisulfite modification and whole-genome amplification was performed. Promoter methylation levels of APC(me), FOXA1(me), GSTP1(me), HOXD3(me), RARβ2(me), RASSF1A(me), SEPT9(me) and SOX17(me) were assessed by multiplex quantitative methylation-specific PCR. SEPT9(me) and SOX17(me) were the only biomarkers shared by all three cancer types, although they detected CRC with limited sensitivity. A “PanCancer” panel (FOXA1(me), RARβ2(me) and RASSF1A(me)) detected LC and PCa with 64% sensitivity and 70% specificity, complemented with “CancerType” panel (GSTP1(me) and SOX17(me)) which discriminated between LC and PCa with 93% specificity, but with modest sensitivity. Moreover, a HOXD3(me) and RASSF1A(me) panel discriminated small cell lung carcinoma from non-small cell lung carcinoma with 75% sensitivity, 88% specificity, 6.5 LR+ and 0.28 LR–. An APC(me) and RASSF1A(me) panel independently predicted disease-specific mortality in LC patients. CONCLUSIONS: 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. |
format | Online Article Text |
id | pubmed-6889617 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-68896172019-12-11 Early detection of the major male cancer types in blood-based liquid biopsies using a DNA methylation panel Constâncio, Vera Nunes, Sandra P. Moreira-Barbosa, Catarina Freitas, Rui Oliveira, Jorge Pousa, Inês Oliveira, Júlio Soares, Marta Dias, Carlos Gonçalves Dias, Teresa Antunes, Luís Henrique, Rui Jerónimo, Carmen Clin Epigenetics Research BACKGROUND: Lung (LC), prostate (PCa) and colorectal (CRC) cancers are the most incident in males worldwide. 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. RESULTS: Circulating cell-free DNA was extracted from 102 LC, 121 PCa and 100 CRC patients and 136 asymptomatic donors’ plasma samples. Sodium-bisulfite modification and whole-genome amplification was performed. Promoter methylation levels of APC(me), FOXA1(me), GSTP1(me), HOXD3(me), RARβ2(me), RASSF1A(me), SEPT9(me) and SOX17(me) were assessed by multiplex quantitative methylation-specific PCR. SEPT9(me) and SOX17(me) were the only biomarkers shared by all three cancer types, although they detected CRC with limited sensitivity. A “PanCancer” panel (FOXA1(me), RARβ2(me) and RASSF1A(me)) detected LC and PCa with 64% sensitivity and 70% specificity, complemented with “CancerType” panel (GSTP1(me) and SOX17(me)) which discriminated between LC and PCa with 93% specificity, but with modest sensitivity. Moreover, a HOXD3(me) and RASSF1A(me) panel discriminated small cell lung carcinoma from non-small cell lung carcinoma with 75% sensitivity, 88% specificity, 6.5 LR+ and 0.28 LR–. An APC(me) and RASSF1A(me) panel independently predicted disease-specific mortality in LC patients. CONCLUSIONS: 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. BioMed Central 2019-12-02 /pmc/articles/PMC6889617/ /pubmed/31791387 http://dx.doi.org/10.1186/s13148-019-0779-x Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Constâncio, Vera Nunes, Sandra P. Moreira-Barbosa, Catarina Freitas, Rui Oliveira, Jorge Pousa, Inês Oliveira, Júlio Soares, Marta Dias, Carlos Gonçalves Dias, Teresa Antunes, Luís Henrique, Rui Jerónimo, Carmen Early detection of the major male cancer types in blood-based liquid biopsies using a DNA methylation panel |
title | Early detection of the major male cancer types in blood-based liquid biopsies using a DNA methylation panel |
title_full | Early detection of the major male cancer types in blood-based liquid biopsies using a DNA methylation panel |
title_fullStr | Early detection of the major male cancer types in blood-based liquid biopsies using a DNA methylation panel |
title_full_unstemmed | Early detection of the major male cancer types in blood-based liquid biopsies using a DNA methylation panel |
title_short | Early detection of the major male cancer types in blood-based liquid biopsies using a DNA methylation panel |
title_sort | early detection of the major male cancer types in blood-based liquid biopsies using a dna methylation panel |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6889617/ https://www.ncbi.nlm.nih.gov/pubmed/31791387 http://dx.doi.org/10.1186/s13148-019-0779-x |
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