Epigenetic quantification of circulating immune cells in peripheral blood of triple-negative breast cancer patients

Clinical Epigenetics

Clarissa Gerhäuser¹  Yon-Dschun Ko²  Thomas Hielscher³  Hiltrud Brauch⁴  Thomas Brüning⁵  Ute Hamann⁶  Nasim Borhani⁶  Mehdi Manoochehri⁷  Olivia Fletcher⁸  Anthony J. Swerdlow⁹ 

[1]Cancer Epigenomics, German Cancer Research Center (DKFZ), Heidelberg, Germany

[2]Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, 53113, Bonn, Germany

[3]Division of Biostatistics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany

[4]Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, 70376, Stuttgart, Germany

[5]iFIT Cluster of Excellence, University of Tübingen, 72074, Tübingen, Germany

[6]German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Partner Site Tübingen, 72074, Tübingen, Germany

[7]Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), 44789, Bochum, Germany

[8]Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, 69120, Heidelberg, Germany

[9]Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, 69120, Heidelberg, Germany

[10]Department of in-Vitro Diagnostics, Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB, Stuttgart, Germany

[11]The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, UK

[12]The Institute of Cancer Research, London, UK

[13]Division of Genetics and Epidemiology and Division of Breast Cancer Research, The Institute of Cancer Research, London, UK

关键词: Triple-negative breast cancer;    DNA methylation in blood;    Immune cell subtypes;    TNBC risk;   

DOI  :  10.1186/s13148-021-01196-1

来源: Springer

【 摘 要 】

BackgroundA shift in the proportions of blood immune cells is a hallmark of cancer development. Here, we investigated whether methylation-derived immune cell type ratios and methylation-derived neutrophil-to-lymphocyte ratios (mdNLRs) are associated with triple-negative breast cancer (TNBC).MethodsLeukocyte subtype-specific unmethylated/methylated CpG sites were selected, and methylation levels at these sites were used as proxies for immune cell type proportions and mdNLR estimation in 231 TNBC cases and 231 age-matched controls. Data were validated using the Houseman deconvolution method. Additionally, the natural killer (NK) cell ratio was measured in a prospective sample set of 146 TNBC cases and 146 age-matched controls.ResultsThe mdNLRs were higher in TNBC cases compared with controls and associated with TNBC (odds ratio (OR) range (2.66–4.29), all Padj. < 1e−04). A higher neutrophil ratio and lower ratios of NK cells, CD4 + T cells, CD8 + T cells, monocytes, and B cells were associated with TNBC. The strongest association was observed with decreased NK cell ratio (OR range (1.28–1.42), all Padj. < 1e−04). The NK cell ratio was also significantly lower in pre-diagnostic samples of TNBC cases compared with controls (P = 0.019).ConclusionThis immunomethylomic study shows that a shift in the ratios/proportions of leukocyte subtypes is associated with TNBC, with decreased NK cell showing the strongest association. These findings improve our knowledge of the role of the immune system in TNBC and point to the possibility of using NK cell level as a non-invasive molecular marker for TNBC risk assessment, early detection, and prevention.

【 授权许可】

CC BY