Breast cancer risk assessment: a non-invasive multiparametric approach to stratify patients by MMP-9 serum activity and RhoA expression patterns in circulating leucocytes.
Breast cancer is a multifactorial disease classified by several sub-types which differ from each other by risk factors, specific molecular promoters and severity of outcomes. Tumour aggressiveness and metastatic disease are the key determinants of breast cancer outcomes. Tumour cell ability to degrade the extracellular matrix and to be motile is the hallmark of invasion and essential step in a development of breast cancer metastatic disease. Therefore, a coordinated action between cell motility and ability to degrade the extracellular matrix is currently under extensive investigation focused on molecular targets for both diagnostic and therapeutic purposes. Contextually, our current study was dedicated to patient stratification utilising MMP-9 serum activity levels and RhoA expression patterns measured in circulating leucocytes. Biomarker patterns were "masked" in non-stratified patient groups. In contrast, the multiparametric stratification approach led to highly improved clinical utility of biomarker patterns. Presented stratification system is recommended for population screening as a cost-effective non-invasive approach to facilitate predictive diagnostics of breast cancer predisposition, pre-lesions and early stages, when the pathology can be effectively prevented or cured. Proposed approach might be particularly useful for early and predictive breast cancer diagnostics applied to certain phenotypes such as premenopausal rather than postmenopausal women, women with dense breast tissue, where highly increased RhoA/MMPs activities are utilised for effective proteolysis of the matrix and cancer cell migration into dense matrices, as well as for breast cancer of unclear origin such as particularly aggressive triple-negative sub-type.
Department of Radiology, University of Bonn, Bonn, Germany. olga.golubnitschaja@ukb.uni-bonn.de.|Breast Cancer Research Centre, University of Bonn, Bonn, Germany. olga.golubnitschaja@ukb.uni-bonn.de.|European Association for Predictive, Preventive and Personalised Medicine (EPMA), Brussels, Belgium. olga.golubnitschaja@ukb.uni-bonn.de.
Olga
http://orcid.org/0000-0001-5427-2018
O
Golubnitschaja
Department of Radiology, University of Bonn, Bonn, Germany.|Breast Cancer Research Centre, University of Bonn, Bonn, Germany.|European Association for Predictive, Preventive and Personalised Medicine (EPMA), Brussels, Belgium.
Kristina
K
Yeghiazaryan
Department of Radiology, University of Bonn, Bonn, Germany.|Breast Cancer Research Centre, University of Bonn, Bonn, Germany.|European Association for Predictive, Preventive and Personalised Medicine (EPMA), Brussels, Belgium.
Jella-Andrea
JA
Abraham
Department of Radiology, University of Bonn, Bonn, Germany.|Breast Cancer Research Centre, University of Bonn, Bonn, Germany.
Hans H
HH
Schild
European Association for Predictive, Preventive and Personalised Medicine (EPMA), Brussels, Belgium.
Vincenzo
V
Costigliola
Breast Cancer Research Centre, University of Bonn, Bonn, Germany.|Department of Obstetrics and Gynaecology, Centre for Integrated Oncology, University of Bonn, Bonn, Germany.
Manuel
M
Debald
Breast Cancer Research Centre, University of Bonn, Bonn, Germany.|European Association for Predictive, Preventive and Personalised Medicine (EPMA), Brussels, Belgium.|Department of Obstetrics and Gynaecology, Centre for Integrated Oncology, University of Bonn, Bonn, Germany.
Walther
W
Kuhn
D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism; D001941:Breast Diseases / Q000473:pathology; D001943:Breast Neoplasms / Q000097:blood* / Q000175:diagnosis; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008875:Middle Aged; D017698:Postmenopause; D017697:Premenopause; D018570:Risk Assessment / Q000379:methods; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
D014408:Biomarkers, Tumor; C066737:RHOA protein, human; D020780:Matrix Metalloproteinase 9; D020742:rhoA GTP-Binding Protein
Benignant breast alteration; Biomarker pattern; Blood test; Breast cancer; Metalloproteinase 9; Metastatic disease; Molecular targets; Patient stratification; Predictive medicine; Rho GTPase