Comparative Analysis of Molecular Functions and Biological Role of Proteins from Cell-Free DNA-Protein Complexes Circulating in Plasma of Healthy Females and Breast Cancer Patients

Tutanov, Oleg; Shefer, Aleksei; Tsentalovich, Yuri P.; Тамкович, С. Н.

doi:10.3390/ijms24087279

Cited by 2 publications

(5 citation statements)

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“…In independent studies of DNA kinetic analysis, size and ends profiling [25,[39][40][41], strong evidence has been obtained that part of the cell-free DNA is a product of active cellular secretion. Our results on the protein composition of NPC that were analyzed by STRING 12.0 software after identification of proteins indirectly confirm the data of these authors: in BCP blood, the representation of apoptosis proteins decreases and the representation of proteins involved in secretion processes increases [32]. The absence of necrosis-associated proteins in NPC in the blood of BCPs at stage I of the disease seems logical, since necrotic processes in malignant pathologies are characteristic of the terminal stages, when severe ischemia of tumor tissues is observed.…”

Section: Discussionsupporting

confidence: 88%

“…Blood plasma histone-containing NPCs were isolated using affine chromatography, as previously described [32]. Briefly, venous blood (9 mL) was collected in K3EDTA spraycoated vacutainers (Improvacuter, China, cat.…”

Section: The Isolation Of Histone-containing Npc From Blood Plasmamentioning

confidence: 99%

“…However, the share of DNA in the NPCs from cfDNA in blood plasma in HFs and BCPs did not differ significantly, nor did the share of NPC protein from blood plasma total protein. Moreover, bioinformatic analysis after identification of proteins by MALDI-TOF mass spectrometry revealed that, in the presence of a malignant tumor, the proportion of proteins involved in ion channels, protein binding, transport, and signal transduction increased in the composition of blood-circulating NPCs [32]. Since the composition of NPCs can include not only DNA-binding proteins, but also proteins that interact with such proteins but do not bind DNA (passenger proteins), the questions about the significance of those proteins in blood NPCs remains open.…”

Section: Introductionmentioning

confidence: 99%

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DNA-Binding Proteins and Passenger Proteins in Plasma DNA–Protein Complexes: Imprint of Parental Cells or Key Mediators of Carcinogenesis Processes?

Tutanov,

Shefer,

Shefer

et al. 2024

IJMS

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Knowledge of the composition of proteins that interact with plasma DNA will provide a better understanding of the homeostasis of circulating nucleic acids and the various modes of interaction with target cells, which may be useful in the development of gene targeted therapy approaches. The goal of the present study is to shed light on the composition and architecture of histone-containing nucleoprotein complexes (NPCs) from the blood plasma of healthy females (HFs) and breast cancer patients (BCPs) and to explore the relationship of proteins with crucial steps of tumor progression: epithelial–mesenchymal transition (EMT), cell proliferation, invasion, cell migration, stimulation of angiogenesis, and immune response. MALDI-TOF mass spectrometric analysis of NPCs isolated from blood samples using affine chromatography was performed. Bioinformatics analysis showed that the shares of DNA-binding proteins in the compositions of NPCs in normal and cancer patients are comparable and amount to 40% and 33%, respectively; in total, we identified 38 types of DNA-binding motifs. Functional enrichment analysis using FunRich 3.13 showed that, in BCP blood, the share of DNA-binding proteins involved in nucleic acid metabolism increased, while the proportion of proteins involved in intercellular communication and signal transduction decreased. The representation of NPC passenger proteins in breast cancer also changes: the proportion of proteins involved in transport increases and the share of proteins involved in energy biological pathways decreases. Moreover, in the HF blood, proteins involved in the processes of apoptosis were more represented in the composition of NPCs and in the BCP blood—in the processes of active secretion. For the first time, bioinformatics approaches were used to visualize the architecture of circulating NPCs in the blood and to show that breast cancer has an increased representation of passenger proteins involved in EMT, cell proliferation, invasion, cell migration, and immune response. Using breast cancer protein data from the Human Protein Atlas (HPA) and DEPC, we found that 86% of NPC proteins in the blood of BCPs were not previously annotated in these databases. The obtained data may indirectly indicate directed protein sorting in NPCs, which, along with extracellular vesicles, can not only be diagnostically significant molecules for liquid biopsy, but can also carry out the directed transfer of genetic material from donor cells to recipient cells.

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Section: Discussionsupporting

confidence: 88%

Section: The Isolation Of Histone-containing Npc From Blood Plasmamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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DNA-Binding Proteins and Passenger Proteins in Plasma DNA–Protein Complexes: Imprint of Parental Cells or Key Mediators of Carcinogenesis Processes?

Tutanov,

Shefer,

Shefer

et al. 2024

IJMS

Self Cite

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“…No. 694091210), and processed as described previously [21]. The absence of hemolysis/lysis of blood cells was confirmed through the determination of LDH levels using the LDH kit as recommended by the manufacturer (Vector-Best Ltd., Novosibirsk, Russia); samples with signs of hemolysis were excluded from the study.…”

Section: Blood Samplesmentioning

confidence: 99%

“…An affine sorbent with immobilized anti-histone antibodies was synthesized as described previously [21]. Histone-containing NPCs were isolated from individual plasma samples (0.8 mL) by affinity chromatography, and the NPC samples were concentrated as described previously [21].…”

Section: Histone-contained Npc Isolation By Affinity Chromatographymentioning

confidence: 99%

Blood Plasma Circulating DNA-Protein Complexes: Involvement in Carcinogenesis and Prospects for Liquid Biopsy of Breast Cancer

Shefer,

Tutanov,

Belenikin

et al. 2023

JPM

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Circulating DNA (cirDNA) is a promising tool in translational medicine. However, studies of cirDNA have neglected its association with proteins, despite ample evidence that this interaction may affect the fate of DNA in the bloodstream and its molecular functions. The goal of the current study is to shed light on the differences between the proteomic cargos of histone-containing nucleoprotein complexes (NPCs) from healthy female (HFs) and breast cancer patients (BCPs), and to reveal the proteins involved in carcinogenesis. NPCs were isolated from the blood samples of HFs and BCPs using affinity chromatography. A total of 177 and 169 proteins were identified in NPCs from HFs and BCPs using MALDI-TOF mass spectrometry. A bioinformatics analysis revealed that catalytically active proteins, as well as proteins that bind nucleic acids and regulate the activity of receptors, are the most represented among the unique proteins of blood NPCs from HFs and BCPs. In addition, the proportion of proteins participating in ion channels and proteins binding proteins increases in the NPCs from BCP blood. However, the involvement in transport and signal transduction was greater in BCP NPCs compared to those from HFs. Gene ontology term (GO) analysis revealed that the NPC protein cargo from HF blood was enriched with proteins involved in the negative regulation of cell proliferation, and in BCP blood, proteins involved in EMT, invasion, and cell migration were observed. The combination of SPG7, ADRB1, SMCO4, PHF1, and PSMG1 NPC proteins differentiates BCPs from HFs with a sensitivity of 100% and a specificity of 80%. The obtained results indirectly indicate that, in tandem with proteins, blood cirDNA is an important part of intercellular communication, playing a regulatory and integrating role in the physiology of the body.

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Comparative Analysis of Molecular Functions and Biological Role of Proteins from Cell-Free DNA-Protein Complexes Circulating in Plasma of Healthy Females and Breast Cancer Patients

Cited by 2 publications

References 48 publications

DNA-Binding Proteins and Passenger Proteins in Plasma DNA–Protein Complexes: Imprint of Parental Cells or Key Mediators of Carcinogenesis Processes?

DNA-Binding Proteins and Passenger Proteins in Plasma DNA–Protein Complexes: Imprint of Parental Cells or Key Mediators of Carcinogenesis Processes?

Blood Plasma Circulating DNA-Protein Complexes: Involvement in Carcinogenesis and Prospects for Liquid Biopsy of Breast Cancer

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