Introduction: Mammography is the gold standard for early breast cancer detection, but shows important limitations. Blood-based approaches on basis of cell-free DNA (cfDNA) provide minimally invasive screening tools to characterize epigenetic alterations of tumor suppressor genes and could serve as a liquid biopsy, complementing mammography.
Methods: Potential biomarkers were identified from The Cancer Genome Atlas (TCGA), using HumanMethylation450-BeadChip data. Promoter methylation status was evaluated quantitatively by pyrosequencing in a serum test cohort ( 103), a serum validation cohort ( 368) and a plasma cohort ( 125).
Results: , and were identified as novel biomarker candidates. was included on basis of our previous work. In the serum test cohort, a panel of and showed 63% sensitivity for DCIS and 51% sensitivity for early invasive tumor (pT1, pN0) detection at 80% specificity. The serum validation cohort revealed 50% sensitivity for DCIS detection on basis of and . Furthermore, an inverse correlation between methylation frequency and cfDNA concentration was uncovered. Therefore, markers were tested in a plasma cohort, achieving a 64% sensitivity for breast cancer detection using , and .
Conclusions: Although liquid biopsy remains challenging, a combination of , , and (SNiPER) provides a promising tool for blood-based breast cancer detection.
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| http://dx.doi.org/10.18632/oncotarget.27303 | DOI Listing |
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