Journal
CANCERS
Volume 10, Issue 10, Pages -Publisher
MDPI
DOI: 10.3390/cancers10100357
Keywords
breast cancer; colorectal cancer; lung cancer; DNA methylation; epigenetic biomarker; cell-free DNA; liquid biopsy; detection
Categories
Funding
- Research Center of Portuguese Oncology Institute of Porto [PI 74-CI-IPOP-19-2016]
- Nucleo Regional da Madeira da Liga Portuguesa Contra o Cancro & Diario de Noticias
- [IPO/ESTIMA-1 NORTE-01-0145-FEDER-000027]
- [PI 110-CI-IPOP89 2018-CES 329-017]
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Background: Breast (BrC), colorectal (CRC) and lung (LC) cancers are the three most common and deadly cancers in women. Cancer screening entails an increase in early stage disease detection but is hampered by high false-positive rates and overdiagnosis /overtreatment. Aberrant DNA methylation occurs early in cancer and may be detected in circulating cell-free DNA (ccfDNA), constituting a valuable biomarker and enabling non-invasive testing for cancer detection. We aimed to develop a ccfDNA methylation-based test for simultaneous detection of BrC, CRC and LC. Methods: CcfDNA from BrC, CRC and LC patients and asymptomatic controls were extracted from plasma, sodium-bisulfite modified and whole-genome amplified. APC, FOXA1, MGMT, RAR beta 2, RASSF1A, SCGB3A1, SEPT9, SHOX2 and SOX17 promoter methylation levels were determined by multiplex quantitative methylation-specific PCR. Associations between methylation and standard clinicopathological parameters were assessed. Biomarkers' diagnostic performance was also evaluated. Results: A PanCancer panel (APC, FOXA1, RASSF1A) detected the three major cancers with 72% sensitivity and 74% specificity, whereas a CancerType panel (SCGB3A1, SEPT9 and SOX17) indicated the most likely cancer topography, with over 80% specificity, although with limited sensitivity. Conclusions: CcfDNA's methylation assessment allows for simultaneous screening of BrC, CRC and LC, complementing current modalities, perfecting cancer suspects' triage, increasing compliance and cost-effectiveness.
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