IntroductionMammography 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.MethodsPotential 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.
ConclusionsAlthough liquid biopsy remains challenging, a combination of SPAG6, NKX2-6, ITIH5 and PER1 (SNiPER) provides a promising tool for blood-based breast cancer detection.
The study found that the majority of questioned trainers are still using the principles taught in the course successfully with persons with dementia living at home and the content was found to be relevant for practice. The content of the teaching course, applying principles of retrogenesis, which was originally designed for persons with dementia living at home, can also be successfully applied in the nursing home environment. Increasing interest has been shown by institutions employing professionals whose task it is to keep persons with dementia active and interested as well as physically functioning at their best possible level. As a consequence, persons with dementia perceive higher quality of life and exhibit fewer behavior problems which complicate care. More research is needed to accumulate evidence and to support these findings.
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