TY - JOUR

T1 - The Composition of Small Extracellular Vesicles (sEVs) in the Blood Plasma of Colorectal Cancer Patients Reflects the Presence of Metabolic Syndrome and Correlates with Angiogenesis and the Effectiveness of Thermoradiation Therapy

AU - Yunusova, Natalia V

AU - Svarovsky, Dmitry A

AU - Konovalov, Artem I

AU - Kostromitsky, Dmitry N

AU - Startseva, Zhanna A

AU - Cheremisina, Olga V

AU - Afanas'ev, Sergey G

AU - Kondakova, Irina V

AU - Grigor'eva, Alina E

AU - Vtorushin, Sergey V

AU - Sereda, Elena E

AU - Usova, Anna V

AU - Tamkovich, Svetlana N

N1 - Funding: This research was funded by the grant Russian Science Foundation N 23-25-00085, https://rscf.ru/project/23-25-00085/ accessed on 17 January 2023.

PY - 2023/4/19

Y1 - 2023/4/19

N2 - The majority of colorectal cancer patients (CRCPs) develop tumors on the background of "metabolically healthy obesity" or metabolic syndrome. The aim of the work was to study the levels of matrix metalloproteinases (MMPs) and heat shock proteins (HSPs) on the surface of blood plasma CD9-positive and FABP4-positive small extracellular vesicles (sEVs) from CRCPs depending on metabolic status and tumor angiogenesis, as well as to evaluate the sEVs markers as predictors of the effectiveness of thermoradiotherapy. In CRCPs, compared with patients with colorectal polyps (CPPs), the proportion of triple positive EVs and EVs with the MMP9+MMP2-TIMP1+ phenotype increased significantly among FABP4-positive EVs (adipocyte-derived EVs), which in general may indicate the overexpression of MMP9 and TIMP1 by adipocytes or adipose tissue macrophages in CRCPs. The results obtained have prospects for use as markers to clarify cancer risk in CPPs. One can assume that for CRCPs with metabolic syndrome or metabolically healthy obesity, it is the FABP4+MMP9+MMP2-TIMP1- population of circulating sEVs that is the most optimal biomarker reflecting tumor angiogenesis. Determining this population in the blood will be useful in monitoring patients after treatment for the early detection of tumor progression. CD9+MMP9+MMP2-TIMP1- and MMP9+MMP2-TIMP1+ subpopulations of circulating sEVs are the most promising predictors of the efficacy of thermoradiation therapy because their levels at baseline differ significantly in CRCPs with different tumor responses.

AB - The majority of colorectal cancer patients (CRCPs) develop tumors on the background of "metabolically healthy obesity" or metabolic syndrome. The aim of the work was to study the levels of matrix metalloproteinases (MMPs) and heat shock proteins (HSPs) on the surface of blood plasma CD9-positive and FABP4-positive small extracellular vesicles (sEVs) from CRCPs depending on metabolic status and tumor angiogenesis, as well as to evaluate the sEVs markers as predictors of the effectiveness of thermoradiotherapy. In CRCPs, compared with patients with colorectal polyps (CPPs), the proportion of triple positive EVs and EVs with the MMP9+MMP2-TIMP1+ phenotype increased significantly among FABP4-positive EVs (adipocyte-derived EVs), which in general may indicate the overexpression of MMP9 and TIMP1 by adipocytes or adipose tissue macrophages in CRCPs. The results obtained have prospects for use as markers to clarify cancer risk in CPPs. One can assume that for CRCPs with metabolic syndrome or metabolically healthy obesity, it is the FABP4+MMP9+MMP2-TIMP1- population of circulating sEVs that is the most optimal biomarker reflecting tumor angiogenesis. Determining this population in the blood will be useful in monitoring patients after treatment for the early detection of tumor progression. CD9+MMP9+MMP2-TIMP1- and MMP9+MMP2-TIMP1+ subpopulations of circulating sEVs are the most promising predictors of the efficacy of thermoradiation therapy because their levels at baseline differ significantly in CRCPs with different tumor responses.

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85154541640&origin=inward&txGid=4e0cea84507cd8dd9d7b0dbfd6d9fa78

U2 - 10.3390/jpm13040684

DO - 10.3390/jpm13040684

M3 - Article

C2 - 37109070

VL - 13

JO - Journal of Personalized Medicine

JF - Journal of Personalized Medicine

SN - 2075-4426

IS - 4

M1 - 684

ER -