Sniper: A novel hypermethylation biomarker panel for liquid biopsy based early breast cancer detection

Mijnes J, Tiedemann J, Eschenbruch J, Gasthaus J, Bringezu S, Bauerschlag D, Maass N, Arnold N, Weimer J, Anzeneder T, Fasching P, Rübner M, Bruno B, Heindrichs U, Freres J, Schulz H, Hilgers RD, Ortiz-Brüchle N, Von Serenyi S, Knüchel R, Kloten V, Dahl E (2019)

Publication Type: Journal article

Publication year: 2019

Journal

Oncotarget Impact Journals

Book Volume: 10

Pages Range: 6494-6508

Journal Issue: 60

Abstract

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.

Authors with CRIS profile

Peter Fasching Professur für Translationale Frauenheilkunde und Geburtshilfe Matthias Rübner Department of Obstetrics and Gynaecology

Involved external institutions

Universitätsklinikum Aachen (UKA) DE Germany (DE) Universitätsklinikum Schleswig-Holstein (UKSH) DE Germany (DE) Luisenhospital Aachen DE Germany (DE) Technische Universität München (TUM) DE Germany (DE)

How to cite

APA:

Mijnes, J., Tiedemann, J., Eschenbruch, J., Gasthaus, J., Bringezu, S., Bauerschlag, D.,... Dahl, E. (2019). Sniper: A novel hypermethylation biomarker panel for liquid biopsy based early breast cancer detection. Oncotarget, 10(60), 6494-6508.

MLA:

Mijnes, Jolein, et al. "Sniper: A novel hypermethylation biomarker panel for liquid biopsy based early breast cancer detection." Oncotarget 10.60 (2019): 6494-6508.

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