Evaluation of Extracellular Matrix Biomarkers in Colorectal Carcinoma

Extracellular matrix, which constitutes the majority of tumor stroma, plays a leading role in the progression of various cancers, including colorectal carcinoma, and, therefore, contributes to the creation of an environment conducive to metastasis. The aim of this work was to study the clinical significance of the immunohistochemical activity of metalloproteinases (MMP-9, MMP-12) and proangiogenic factors (HIFa, VEGF-A, Ang1, Ang2) and to identify their relationship with the clinical and morphological characteristics and prognosis of colorectal cancer (CRC). Material and methods. For the study, histological material was collected from patients with verified colorectal carcinoma (n=263). All patients were divided into two groups: 1st - with metastatic colorectal cancer (n=132); 2nd - with non-metastatic colorectal cancer (n=131). The study material was tumor tissue fragments obtained during surgery for subsequent histological and immunohistochemical studies with markers of metalloproteinases type 9, 12 (MMP12, MMP9), vascular endothelial growth factor (VEGF-A), hypoxia-inducible factor-1Α (HIF1α), angiopoietins type 1 and 2 (Ang1, Ang2). Evaluation of the expression of metalloproteinases and proangiogenic factors confirmed their clinical significance in the progression of neoplastic processes. Results.The obtained data on the close functional relationship between proangiogenic factors and metalloproteinases indicate the promise of their use as prognostic biomarkers. It is assumed that the determination of these markers will identify a subclass of patients with a higher risk of recurrence/progression of colorectal carcinoma. Thus, the use of immunohistochemical diagnostic methods that determine the expression of such markers as: MMP12, MMP9, HIFa, VEGF-A, Ang1, Ang2 with an assessment of the intensity of the reaction and the correlation between them, opens up new prospects in oncodiagnostics. Conclusion. Conducting the recommended diagnostic studies will not only predict the prognosis of the disease, but will also help with the further determination of therapeutic tactics.