Abstract
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, RARβ2, 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.
Highlights
Breast (BrC), colorectal (CRC) and lung (LC) cancers are the most incident and lethal malignancies affecting women from developed countries [1]
We aimed to develop a sensitive and specific methylation-based test enabling the simultaneous detection of breast cancer (BrC), CRC and lung cancer (LC) in women using circulating cell-free DNA (ccfDNA)
SOX17 promoter has been reported as aberrantly methylated in ccfDNA and CTCs from BrC patients’ [35], albeit its
Summary
Breast (BrC), colorectal (CRC) and lung (LC) cancers are the most incident and lethal malignancies affecting women from developed countries [1]. Colonoscopy-based screening is performed every ten years after the age of 50 years [7], displaying high sensitivity and the main advantage of removing lesions at the time of detection [7]. It is an invasive and costly procedure, requiring unpleasant bowel preparation, sedation, the risk of bowel perforation, bleeding, and low compliance [7]. Cancer screening entails an increase in early stage disease detection but is hampered by high false-positive rates and overdiagnosis/overtreatment. 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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