TY - JOUR

T1 - Exosomal Protease Cargo as Prognostic Biomarker in Colorectal Cancer

AU - Yunusova, Natalia V.

AU - Zambalova, Elena A.

AU - Patysheva, Marina R.

AU - Kolegova, Elena S.

AU - Afanas’ev, Sergey G.

AU - Cheremisina, Olga V.

AU - Grigor’eva, Alina E.

AU - Tamkovich, Svetlana N.

AU - Kondakova, Irina V.

N1 - Funding Information: This work supported by the Russian Foundation for Basic Research and the Government of Tomsk region, grant 18-415-703006. Publisher Copyright: © 2021. All Rights Reserved.

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

KW - 20S proteasome

KW - CD151

KW - colorectal cancer

KW - metalloproteinases

KW - Plasma exosomes

KW - Prognosis

KW - Proteasome Endopeptidase Complex/metabolism

KW - Colonic Polyps/enzymology

KW - Humans

KW - Middle Aged

KW - Male

KW - Peptide Hydrolases/metabolism

KW - Exosomes/enzymology

KW - Tetraspanin 24/metabolism

KW - Neoplasm Grading

KW - Colorectal Neoplasms/enzymology

KW - Female

KW - Basigin/metabolism

KW - Carcinoma/enzymology

KW - Matrix Metalloproteinase 2/metabolism

KW - Matrix Metalloproteinase 9/metabolism

KW - Tetraspanins/metabolism

KW - Intestinal Polyps/enzymology

KW - Adenoma, Villous/enzymology

KW - Adenoma/enzymology

KW - Neoplasm Staging

UR - http://www.scopus.com/inward/record.url?scp=85103483848&partnerID=8YFLogxK

UR - https://www.elibrary.ru/item.asp?id=46771479

U2 - 10.31557/APJCP.2021.22.3.861

DO - 10.31557/APJCP.2021.22.3.861

M3 - Article

C2 - 33773551

AN - SCOPUS:85103483848

VL - 22

SP - 861

EP - 869

JO - Asian Pacific Journal of Cancer Prevention

JF - Asian Pacific Journal of Cancer Prevention

SN - 1513-7368

IS - 3

M1 - 3

ER -