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A DNA Methylation-Based Test for Breast Cancer Detection in Circulating Cell-Free DNA.
Journal of Clinical Medicine 2018 November 8
BACKGROUND: Breast cancer (BrC) is the most frequent neoplasm in women. New biomarkers, including aberrant DNA methylation, may improve BrC management. Herein, we evaluated the detection and prognostic performance of seven genes' promoter methylation ( APC , BRCA1 , CCND2 , FOXA1 , PSAT1 , RASSF1A and SCGB3A1 ).
METHODS: Methylation levels were assessed in primary BrC tissues by quantitative methylation-specific polymerase chain reaction (QMSP) and in circulating cell-free DNA (ccfDNA) by multiplex QMSP from two independent cohorts of patients (Cohort #1, n = 137; and Cohort #2, n = 44). Receiver operating characteristic (ROC) curves were constructed, and log-rank test and Cox regression were performed to assess the prognostic value of genes' methylation levels.
RESULTS: The gene-panel APC , FOXA1 , RASSF1A , SCGB3A1 discriminated normal from cancerous tissue with high accuracy (95.55%). In multivariable analysis, high PSAT1 -methylation levels [>percentile 75 (P75)] associated with longer disease-free survival, whereas higher FOXA1 -methylation levels (>P75) associated with shorter disease-specific survival. The best performing panel in ccfDNA ( APC , FOXA1 and RASSF1A ) disclosed a sensitivity, specificity and accuracy over 70%.
CONCLUSIONS: This approach enables BrC accurate diagnosis and prognostic stratification in tissue samples, and allows for early detection in liquid biopsies, thus suggesting a putative value for patient management.
METHODS: Methylation levels were assessed in primary BrC tissues by quantitative methylation-specific polymerase chain reaction (QMSP) and in circulating cell-free DNA (ccfDNA) by multiplex QMSP from two independent cohorts of patients (Cohort #1, n = 137; and Cohort #2, n = 44). Receiver operating characteristic (ROC) curves were constructed, and log-rank test and Cox regression were performed to assess the prognostic value of genes' methylation levels.
RESULTS: The gene-panel APC , FOXA1 , RASSF1A , SCGB3A1 discriminated normal from cancerous tissue with high accuracy (95.55%). In multivariable analysis, high PSAT1 -methylation levels [>percentile 75 (P75)] associated with longer disease-free survival, whereas higher FOXA1 -methylation levels (>P75) associated with shorter disease-specific survival. The best performing panel in ccfDNA ( APC , FOXA1 and RASSF1A ) disclosed a sensitivity, specificity and accuracy over 70%.
CONCLUSIONS: This approach enables BrC accurate diagnosis and prognostic stratification in tissue samples, and allows for early detection in liquid biopsies, thus suggesting a putative value for patient management.
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