Changes of exosomal matrix metalloproteinases level in colorectal cancer associated with sex and metabolic disturbance

The objective is to evaluate the contents of matrix metalloproteinases (MMP) MMP9, MMP2, as well as their inducer EMMPRIN in circulating exosomes of patients with colorectal cancer in relation with clinical and morphological parameters, as well as with the presence of metabolic syndrome to search for promising exosomal markers associated with invasion, metastasis and metabolic disorders.

Materials and methods. The study included 40 patients with colorectal cancer (T2–4N0–2M0–1) and 10 control patients. Exosomes of blood plasma were isolated by ultrafiltration with ultracentrifugation. The level of MMP9, MMP2 and their inducer EMMPRIN in exosomes was evaluated by flow cytometry.

Results and conclusion. The level of MMP9‑positive exosomes was significantly higher in patients with colorectal cancer compared with patients with colorectal polyps. The proportion of MMP9‑negative and triple positive MMP9 + / MMP2+ / EMMPRIN+ exosomes, on the contrary, was higher in patients with polyps compared with patients with colorectal cancer. Mixed subpopulation of MMP9+ / MMP2– / EMMPRIN-exosomes prevailed both in patients with colorectal cancer and in control patients. There were no significant differences in the subpopulations of MMP and EMMPRIN in the exosomes of colorectal cancer patients depending on the age, stage, grade and localization. Gender differences in the occurrence of a triple-positive exosome subpopulation in colorectal cancer patients have been revealed. No relationship was found between the expression of MMP and EMMPRIN in exosomes and the presence of the metabolic syndrome, anthropometric parameters, the level of total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol. However, the relationships between MMP9+ / MMP2– / EMMPRIN–, MMP9+ / MMP2– / EMMPRIN– and the level of triglycerides and glucose in blood serum were revealed. Further studies are needed to study the characteristics of exosomes associated with metabolic disorders and the possibility of their use as diagnostic, prognostic, or predictor biomarkers.

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