Page 57 - SDIR5 Abstract book 21 12 2021.

POSTER PRESENTATIONS

P17

uPA/PAI-1, MMP-2, -9, IL-8 and VEGF as markers of progression in early breast cancer
patients

1
1
1
Nataša Todorović-Raković , Jelena Milovanović , Tijana Vujasinović , Jelena Hranisavljević 2
1 Department of Experimental Oncology, Institute of Oncology and Radiology of Serbia, Belgrade, Serbia
2 Laboratory for Radiobiology and Molecular Genetics, Vinča Institute of Nuclear Sciences, Belgrade, Serbia

Background: Cancer progression and metastasis are complex processes, dependent of molecules involved
in inflammation, degradation and invasion. Interleukin-8 (IL-8) has a role in inflammation, urokinase
plasminogen activator (uPA), plasminogen activator inhibitor type-1 (PAI-1) and matrix metalloproteinase-
2, -9 have a decisive part in the process of degradation and invasion, while vascular endothelial growth
factor (VEGF) is consequential for angiogenesis. This study aimed to evaluate the relations between IL-8,
uPA, PAI-1, MMP-2, MMP-9 and VEGF, as well as their prognostic significance in terms of recurrence free
survival (RFS). Patients and Methods: The study included 91 adjuvantly untreated patients with lymph node
negative primary breast cancer. The follow-up period was 30 months. Biomarker protein concentrations
were determined in primary tumor tissue homogenates by ELISA. Survival curves for RFS were constructed
according to the Kaplan-Meier method and compared with the log-rank test, using an optimal cut-off point
and the minimal p-value approach. Results: Patients with higher concentrations of uPA (>0.286 ng/mg),
PAI-1 (>6.601 ng/mg), IL-8 (>99.27 pg/mg) or MMP-2 (>20.54 ng/mg) had significantly shorter RFS (Log rank
test). Positive correlations were found between uPA and PAI-1 (Spearman’s rank order test, p<0.001), uPA
and MMP-9 (p=0.02), PAI-1 and IL-8 (p=0.03), MMP-9 and IL-8 (p<0.001), MMP-9 and VEGF (p=0.02), IL-8
and VEGF (p=0.01). Conclusion: Higher concentrations of uPA, PAI-1, IL-8 and MMP2 are indicators of
aggressive tumor behavior and poor prognosis. Since they all have the role in tumor progression and could
have related expression pattern (positive correlation), they are perhaps controlled by the same regulators.
Keywords: biomarkers, breast cancer, interleukin 8, matrix metalloproteinases, plasminogen activators,
prognosis.

44