J 2022

Proteomic analysis of the bone marrow microenvironment in extramedullary multiple myeloma patients

GREGOROVÁ, Jana, Petra VYCHYTILOVÁ, Tereza KRAMÁŘOVÁ, Zdenka KNECHTOVA, Martina ALMASI et. al.

Basic information

Original name

Proteomic analysis of the bone marrow microenvironment in extramedullary multiple myeloma patients

Authors

GREGOROVÁ, Jana (203 Czech Republic, belonging to the institution), Petra VYCHYTILOVÁ (203 Czech Republic, belonging to the institution), Tereza KRAMÁŘOVÁ (203 Czech Republic, belonging to the institution), Zdenka KNECHTOVA (203 Czech Republic), Martina ALMASI (203 Czech Republic), Martin ŠTORK (203 Czech Republic), Luděk POUR (203 Czech Republic), Jiří KOHOUTEK (203 Czech Republic, belonging to the institution) and Sabina ŠEVČÍKOVÁ (203 Czech Republic, guarantor, belonging to the institution)

Edition

Neoplasma, Bratislava, Slovenská akademie vied, 2022, 0028-2685

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30204 Oncology

Country of publisher

Slovakia

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Impact factor

Impact factor: 3.000

RIV identification code

RIV/00216224:14110/22:00128264

Organization unit

Faculty of Medicine

UT WoS

000817994000006

Keywords in English

multiple myeloma; extramedullary disease; cytokine; bone marrow microenvironment; protein association network analysis

Tags

International impact, Reviewed
Změněno: 20/2/2023 11:13, Mgr. Tereza Miškechová

Abstract

V originále

Multiple myeloma (MM) is a heterogeneous hematological malignancy characterized by the uncontrolled clonal proliferation of bone marrow (BM) plasma cells. The poor prognosis of patients is associated with the presence of extramedullary disease (EMD). Previously, different mechanisms involved in the colonization of BM niches by MM cells and their escape during EMD have been described. Thus, we aimed to investigate the expression of selected cytokines in the BM plasma of MM patients as well as EMD patients to reveal novel molecules involved in EMD pathogenesis. Expression of 120 different cytokines was measured in BM plasma of 13 MM and 11 EMD patients using Proteome Profiler Antibody Arrays. The correlation between statistically significant cytokines and clinicopathological parameters of patients was determined using the Spearman correlation analysis. Finally, protein-protein interactions were analyzed, and GO and KEGG pathways enrichment analysis was performed. In total, 27 cytokines were found to be differently expressed between MM and EMD patients. After the Benjamini-Hochberg correction for multiple testing, the statistical significance of two cytokines downregulated in EMD (EGF, BDNF) and six cytokines upregulated in EMD (NAP-2, ADIPOQ, CRP, MIG, BAFF, and THBS1) was maintained. Correlation analysis proved a significant association between the expression of these molecules and selected clinical-pathological features of MM/EMD patients. Protein association network analysis revealed important protein-protein interactions between THBS1/EGF, MIG/NAP-2, THBS1/NAP-2, EGF/NAP-2, and ADIPOQ/CRP. Finally, identified cytokines were proved to be significantly involved in focal adhesion, PI3K/AKT, and MAPK signaling pathways, and regulation of cell development, localization, proliferation, migration, differentiation, immune system processes, and stress response. Obtained results confirm the key function of the BM microenvironment in the pathogenesis of MM and indicate the essential role of numerous cytokines in disease progression and EMD development. However, the exact mechanisms need to be further clarified.

Links

MUNI/A/1391/2021, interní kód MU
Name: Molekulární, buněčná, tkáňová a systémová patofyziologie vybraných komplexních nemocí (Acronym: KOMPLEX_PF)
Investor: Masaryk University
NV17-29343A, research and development project
Name: Analýza mikroprostředí kostní dřeně u extramedulárního relapsu mnohočetného myelomu