RESUMEN
OBJECTIVE: The aim of the study was to develop a model for predicting cancer risk in colorectal polyps' patients (CPPs), as well as to reveal additional prognosis factors for Stage III colorectal cancer based on differences in subpopulations of tetraspanins, tetraspanin-associated and tetraspanin-non-associated proteases in blood plasma exosomes of CPPs and colorectal cancer patients (CRCPs). METHODS: The subpopulations of CD151- and Tspan8-positive exosomes, the subpopulations of metalloproteinase at the surface of СD9-positive exosomes and the level of 20S proteasomes in plasma exosomes in 15 CPPs (tubulovillous adenomas) and 60 CRCPs were evaluated using flow cytometry and Western blotting. Logistic regression analysis was performed to predict cancer risk of CPPs. RESULTS: The levels of 20S proteasomes in exosomes, MMP9+, MMP9+/MMP2+/EMMPRIN+ in CD9-positive blood plasma exosomes are associated with the risk of malignant transformation of colorectal tubulovillous adenomas. In patients with Stage III CRC, the levels of 20S proteasomes (less than 2 units) and MMP9+ subpopulations (more than 61%) in plasma exosomes are unfavorable prognostic factors for overall survival. The levels of 20S proteasomes and ADAM10+/ADAM17- subpopulations in CD9-positive blood plasma exosomes are the most significant values for predicting relapse-free survival. CONCLUSION: Protease cargo in CD9-positive blood plasma exosomes is prognostic biomarker for colorectal polyps and colorectal cancer.
Asunto(s)
Adenoma/enzimología , Carcinoma/enzimología , Pólipos del Colon/enzimología , Neoplasias Colorrectales/enzimología , Exosomas/enzimología , Complejo de la Endopetidasa Proteasomal/metabolismo , Adenoma/metabolismo , Adenoma/patología , Adenoma Velloso/enzimología , Adenoma Velloso/metabolismo , Adenoma Velloso/patología , Basigina/metabolismo , Carcinoma/metabolismo , Carcinoma/patología , Pólipos del Colon/metabolismo , Pólipos del Colon/patología , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Exosomas/metabolismo , Femenino , Humanos , Pólipos Intestinales/enzimología , Pólipos Intestinales/metabolismo , Pólipos Intestinales/patología , Masculino , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Péptido Hidrolasas/metabolismo , Pronóstico , Tetraspanina 24/metabolismo , Tetraspaninas/metabolismoRESUMEN
Metalloproteinases and their extracellular matrix metalloproteinase inducer (EMMPRIN) play an essential role in the regulation of signaling from growth factors receptors and adhesion molecules, cell motility and extracellular matrix degradation. The aim of the study was to evaluate the relationship between the levels of small extracellular vesicles (sEVs) metalloproteinases, such as ADAM10, ADAM17, MMP2, MMP9 and EMMPRIN and ascites volume and peritoneal canceromatosis index in advanced ovarian cancer patients (OCPs). The subpopulations of metalloproteinases at the surface of sEVs of borderline ovarian tumor patients (BOTPs) (nâ¯=â¯20, 36.5⯱â¯2.5â¯years) and previously untreated advanced OCPs (nâ¯=â¯35, 56.5⯱â¯2.5â¯years) were evaluated using flow cytometry. The metalloproteinase subpopulations of CD9-positive sEVs isolated from plasma of BOTPs and OCPs appeared to be quite similar. However, a significant difference in the expression of ADAM-metalloproteinases in ascites sEVs was found between BOTPs and OCPs. The level of sEVs metalloproteinases in OCPs significantly depended on the ascites volume. A statistically significant relationship between the level of ADAM10+/ADAM17- subpopulation in plasma sEVs and the peritoneal canceromatosis index was found (Râ¯=â¯0.66, pâ¯<â¯.05). The levels of metalloproteinases and EMMPRIN in circulating sEVs, as well as the assessment of individual subpopulations may be promising approaches to OCPs managing.
