Breast cancer risk assessment: a non-invasive multiparametric approach to stratify patients by MMP-9 serum activity and RhoA expression patterns in circulating leucocytes

Abstract

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.

Matrix Metalloproteinase-9 (MMP-9) as a Cancer Biomarker and MMP-9 Biosensors: Recent Advances

“…Another recent study investigated the possibility of utilizing MMP-9 and RhoA level for breast cancer risk assessment through patient stratification [ 107 ]. Using active MMP-9 activity levels in serum and RhoA expression patterns in circulating leucocytes, the authors developed a non-invasive multiparametric approach to stratify patients with breast cancer.…”

Dietary phytochemicals in breast cancer research: anticancer effects and potential utility for effective chemoprevention

“…Consequently, well-designed clinical trials are needed to establish optimal conditions and individualized treatment algorithms for the cost-effective and readily applicable chemoprevention by dietary phytochemicals. In order to reach the goal, multi-professional expertise is essential to explore, create, and implement a comprehensive approach based on the multiomic diagnostics [ 214 , 215 ], individualized patient profiling [ 216 , 217 ], patient stratification by phenotyping and genotyping [ 218 , 219 ], disease modelling, and machine learning [ 220 ] as well as innovative screening programs linked to the targeted preventive measures [ 221 , 222 ]. Current article conforms to the principles of predictive, preventive, and personalized medicine as the medicine of the future [ 223 ].…”

Impaired wound healing: facts and hypotheses for multi-professional considerations in predictive, preventive and personalised medicine

“…To this end, it is notable that the quality of repair processes in general and, in particular, this of wound healing has not been investigated in FS-affected individuals. However, there is a large number of direct and indirect indications which motivates the healing relevant research to be dedicated specifically to the FS affected individuals, namely -Elevated ET-1 and systemic hypoxia typical for FS and detrimental for WH [75,151] -Retinal vein occlusion is frequently demonstrated by FS individuals [150] -At the molecular level, repair processes are diminished and both MMP-2 and MMP-9 are highly activated in FS individuals as well as in FS-affected patients suffering from normal-tension glaucoma; consequently tissues remodelling is altered in this patient cohort [152,153] -Finally, FS may predispose cancer patients to both impaired wound healing and aggressive metastatic disease, due to systemic hypoxic effects and upregulation of MMPs as proposed by dedicated research [149,[154][155][156].…”