Levels of Proangiogenic Molecules and Terminal Complement Complex C5b-9 in the Crown of Circulating sEVs in Patients with Recurrent Glioblastomas: Relationship with Tumor Molecular Characteristics

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Levels of Proangiogenic Molecules and Terminal Complement Complex C5b-9 in the Crown of Circulating sEVs in Patients with Recurrent Glioblastomas: Relationship with Tumor Molecular Characteristics. / Yunusova, Natalia; Tulendinov, Eldar; Svarovsky, Dmitry et al.

In: Current issues in molecular biology, Vol. 47, No. 2, 132, 18.02.2025.

Research output: Contribution to journal › Article › peer-review

BibTeX

@article{86f19f401cfa44c2931441835b8fbfa7,

title = "Levels of Proangiogenic Molecules and Terminal Complement Complex C5b-9 in the Crown of Circulating sEVs in Patients with Recurrent Glioblastomas: Relationship with Tumor Molecular Characteristics",

abstract = "Circulating small extracellular vesicles (sEVs) are emerging as potential biomarkers for glioblastoma progression. This study aimed to compare the levels of matrix metalloproteinases (MMP2 and MMP9), terminal complement complex (C5b-9), and VEGF-A in circulating sEVs in glioblastoma patients (GBMPs) with and without tumor recurrence. Using differential ultracentrifugation, sEVs were isolated from blood samples of GBMPs with no tumor recurrence for over one year (n = 6) and after first relapse (n = 14). The vesicles were characterized and quantified using flow cytometry. In both groups, C5b-9 was predominantly detected on tumor-specific circulating sEVs (glial fibrillary acidic protein (GFAP)-positive sEVs) with high VEGF-A expression, while C5b-9 was significantly less frequent on sEVs with low VEGF-A expression (p < 0.05). GFAP+VEGF+dimMMP2-C5b-9+ vesicles were rarely detected in GBMPs without relapse, suggesting their potential utility as biomarkers for a favorable relapse-free prognosis. In recurrent GBMPs, a positive correlation was observed between GFAP+VEGF+bright MMP2+C5b-9+ sEVs and MGMT gene promoter methylation levels (r = 0.543, p < 0.05). Additionally, a trend toward a negative correlation was found between GFAP+VEGF+bright MMP2+C5b-9- sEVs and mutant p53 expression in primary tumor tissue (r = −0.44, p = 0.114). These findings suggest that sEV profiles may serve as valuable prognostic markers for glioblastoma recurrence and treatment responses.",

keywords = "GFAP, MGMT gene promoter methylation, VEGF-A, extracellular vesicles, glioblastoma recurrence, matrix metalloproteinases, p53, terminal complement complex",

author = "Natalia Yunusova and Eldar Tulendinov and Dmitry Svarovsky and Anastasia Ryabova and Irina Kondakova and Anastasia Ponomaryova and Sergey Vtorushin and Stanislav Tabakaev and Dmitry Korshunov and Tatiana Shtam and Svetlana Tamkovich and Evgeny Choynzonov",

year = "2025",

month = feb,

day = "18",

doi = "10.3390/cimb47020132",

language = "English",

volume = "47",

journal = "Current issues in molecular biology",

issn = "1467-3037",

publisher = "Caister Academic Press",

number = "2",

}

RIS

TY - JOUR

T1 - Levels of Proangiogenic Molecules and Terminal Complement Complex C5b-9 in the Crown of Circulating sEVs in Patients with Recurrent Glioblastomas: Relationship with Tumor Molecular Characteristics

AU - Yunusova, Natalia

AU - Tulendinov, Eldar

AU - Svarovsky, Dmitry

AU - Ryabova, Anastasia

AU - Kondakova, Irina

AU - Ponomaryova, Anastasia

AU - Vtorushin, Sergey

AU - Tabakaev, Stanislav

AU - Korshunov, Dmitry

AU - Shtam, Tatiana

AU - Tamkovich, Svetlana

AU - Choynzonov, Evgeny

PY - 2025/2/18

Y1 - 2025/2/18

N2 - Circulating small extracellular vesicles (sEVs) are emerging as potential biomarkers for glioblastoma progression. This study aimed to compare the levels of matrix metalloproteinases (MMP2 and MMP9), terminal complement complex (C5b-9), and VEGF-A in circulating sEVs in glioblastoma patients (GBMPs) with and without tumor recurrence. Using differential ultracentrifugation, sEVs were isolated from blood samples of GBMPs with no tumor recurrence for over one year (n = 6) and after first relapse (n = 14). The vesicles were characterized and quantified using flow cytometry. In both groups, C5b-9 was predominantly detected on tumor-specific circulating sEVs (glial fibrillary acidic protein (GFAP)-positive sEVs) with high VEGF-A expression, while C5b-9 was significantly less frequent on sEVs with low VEGF-A expression (p < 0.05). GFAP+VEGF+dimMMP2-C5b-9+ vesicles were rarely detected in GBMPs without relapse, suggesting their potential utility as biomarkers for a favorable relapse-free prognosis. In recurrent GBMPs, a positive correlation was observed between GFAP+VEGF+bright MMP2+C5b-9+ sEVs and MGMT gene promoter methylation levels (r = 0.543, p < 0.05). Additionally, a trend toward a negative correlation was found between GFAP+VEGF+bright MMP2+C5b-9- sEVs and mutant p53 expression in primary tumor tissue (r = −0.44, p = 0.114). These findings suggest that sEV profiles may serve as valuable prognostic markers for glioblastoma recurrence and treatment responses.

AB - Circulating small extracellular vesicles (sEVs) are emerging as potential biomarkers for glioblastoma progression. This study aimed to compare the levels of matrix metalloproteinases (MMP2 and MMP9), terminal complement complex (C5b-9), and VEGF-A in circulating sEVs in glioblastoma patients (GBMPs) with and without tumor recurrence. Using differential ultracentrifugation, sEVs were isolated from blood samples of GBMPs with no tumor recurrence for over one year (n = 6) and after first relapse (n = 14). The vesicles were characterized and quantified using flow cytometry. In both groups, C5b-9 was predominantly detected on tumor-specific circulating sEVs (glial fibrillary acidic protein (GFAP)-positive sEVs) with high VEGF-A expression, while C5b-9 was significantly less frequent on sEVs with low VEGF-A expression (p < 0.05). GFAP+VEGF+dimMMP2-C5b-9+ vesicles were rarely detected in GBMPs without relapse, suggesting their potential utility as biomarkers for a favorable relapse-free prognosis. In recurrent GBMPs, a positive correlation was observed between GFAP+VEGF+bright MMP2+C5b-9+ sEVs and MGMT gene promoter methylation levels (r = 0.543, p < 0.05). Additionally, a trend toward a negative correlation was found between GFAP+VEGF+bright MMP2+C5b-9- sEVs and mutant p53 expression in primary tumor tissue (r = −0.44, p = 0.114). These findings suggest that sEV profiles may serve as valuable prognostic markers for glioblastoma recurrence and treatment responses.

KW - GFAP

KW - MGMT gene promoter methylation

KW - VEGF-A

KW - extracellular vesicles

KW - glioblastoma recurrence

KW - matrix metalloproteinases

KW - p53

KW - terminal complement complex

UR - https://www.mendeley.com/catalogue/8cc2e552-bff6-33e2-babe-2cb1e6a5b72f/

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85218868693&origin=inward&txGid=4ad39a3a0e7b4682d9d1c85668f21b90

UR - https://pubmed.ncbi.nlm.nih.gov/39996852/

UR - https://pmc.ncbi.nlm.nih.gov/articles/PMC11854864/

U2 - 10.3390/cimb47020132

DO - 10.3390/cimb47020132

M3 - Article

C2 - 39996852

VL - 47

JO - Current issues in molecular biology

JF - Current issues in molecular biology

SN - 1467-3037

IS - 2

M1 - 132

ER -

ID: 64946404