Biomedical papers, 2017 (vol. 161), issue 3

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2017, 161(3):272-280 | 10.5507/bp.2017.022

Circulating tumor cells and serum levels of MMP-2, MMP-9 and VEGF as markers of the metastatic process in patients with high risk of metastatic progression

Marketa Skerenovaa, Veronika Mikulovaa, Otakar Capounc, Tomas Zimaa, Petra Tesarovab
a Institute of Medical Biochemistry and Laboratory Diagnostics, General University Hospital in Prague and First Faculty of Medicine, Charles University, Prague, Czech Republic
b Department of Oncology, General University Hospital in Prague and First Faculty of Medicine, Charles University, Prague, Czech Republic
c Department of Urology, General University Hospital in Prague and First Faculty of Medicine, Charles University, Prague, Czech Republic Coresponding author: Marketa Skerenova, e-mail: jancikova.market@gmail.com

Background and Aims: Metastases are a severe complication in cancer patients and biomarkers predicting their progression are still lacking for specific groups of patients. HER2 positive breast cancer (HER2 BC) patients on trastuzumab therapy are at risk of the development of unpredictable and often fatal central nervous system (CNS) metastases and castration resistant prostate cancer (CRPC) patients urgently need a marker of disease progression during therapy. Proposed metastatic markers: circulating tumor cells (CTC), serum levels of matrix metalloproteinase 2 (MMP-2), 9 (MMP-9) and vascular endothelial growth factor (VEGF) were prospectively studied to confirm their utility in these two narrowly defined groups of cancer patients.

Patients and Methods: The groups comprised 44 advanced HER2 BC, 24 CRPC patients and 42 healthy controls. An immunomagnetic separation method followed by PCR and electrophoretic detection (AdnaGen, Germany) were used for CTC determination. Serum marker levels were determined by the ELISAs (R&D System, USA).

Results: MMP-2 serum level was significantly higher in HER2 BC patients who developed CNS metastases, especially if there were also bone metastases. CTCs were a negative predictive marker for overall survival in HER2 BC patients. MMP-9 serum level was significantly higher in CRPC patients in whom disease progression occurred. CTC vanished from the blood of most of the CRPC patients (from 88% to 37%) during chemotherapy.

Conclusion: MMP-2 serum level and CTCs show the potential to predict CNS metastases and overall survival in BC patients. CTCs and MMP-9 serum level could be a promising therapy response marker in CRPC patients.

Keywords: cancer biomarkers, circulating tumor cells, matrix metalloproteinases, vascular endothelial growth factor, breast cancers, prostate cancer

Received: December 13, 2016; Accepted: April 28, 2017; Prepublished online: May 16, 2017; Published: September 26, 2017


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