Correction: SNiPER: a novel hypermethylation biomarker panel for liquid biopsy based early breast cancer detection.

[This corrects the article DOI: 10.18632/oncotarget.27303.].

SNiPER: a novel hypermethylation biomarker panel for liquid biopsy based early breast cancer detection.

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 (n = 103), a serum validation cohort (n = 368) and a plasma cohort (n = 125). RESULTS: SPAG6, NKX2-6 and PER1 were identified as novel biomarker candidates. ITIH5 was included on basis of our previous work. In the serum test cohort, a panel of SPAG6 and ITIH5 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 NKX2-6 and ITIH5. 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 SPAG6, PER1 and ITIH5. CONCLUSIONS: Although liquid biopsy remains challenging, a combination of SPAG6, NKX2-6, ITIH5 and PER1 (SNiPER) provides a promising tool for blood-based breast cancer detection.