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
Abstract
:1. Introduction
2. Results
2.1. Concentration of Histones and cfDNA in Plasma of HFs and Untreated BCPs
2.2. Characterization of NPCs Circulating in the Blood Plasma of HFs and BCPs
2.3. Annotation of Identified NPC Proteins
2.4. Characterization of NPC Proteins Involved in Malignant Neoplasms Development
3. Discussion
4. Materials and Methods
4.1. Ethics Statement
4.2. Blood Treatment
4.3. Plasma Histones Measurment
4.4. The Synthesis of Sorbent with Immobilized Anti-Histone Antibodies and NPC Isolation by Affine Chromatography
4.5. Plasma DNA and DNA from NPCs Isolation and Quantification
4.6. MALDI–TOF Mass Spectrometry Analysis
4.7. Bioinformatics and Gene Ontology (GO) Analysis of NPC Proteins
4.8. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Protein Name | Gene Symbol | Protein Function | Expression |
---|---|---|---|
Adenosylhomocysteinase | AHCY | Adenosylhomocysteinase. Has a key role in methylation control. | Hyper-expressed 2 |
Complement factor H-related protein 1 | CFHR1 | Complement factor H-related protein 1. Involved in complement regulation. | |
COP9 signalosome complex subunit 2 | COPS2 | COP9 signalosome complex subunit 2. A key component of a complex involved in several intracellular processes, such as ubiquitination regulation, p53/TP53 phosphorylation, etc. | |
Heat shock protein 105 kDa | HSPH1 | Heat shock protein 105 kDa. Acts as a NEF factor for HSPA1A and HSPA1B. Prevents protein ugregation under stress. | |
Myelin expression factor 2 | MYEF2 | Myelin expression factor 2. Myelin protein expression repressor. | |
Myosin regulatory light chain 12B | MYL12B | Myosin regulatory light chain 12B. Involved in cytokinesis, receptor capping and cell migration. | |
Unconventional myosin-Ic | MYO1C | Myosin-Ic. Involved in intracellular transport. | |
Ran-specific GTPase-activating protein | RANBP1 | Ran-specific GTPase-activating protein. May act in the intracellular signaling pathway, controlling the cell cycle, regulating, protein, and nucleic acid transport across the nuclear membrane | |
60S ribosomal protein L5 | RPL5 | 60S ribosomal protein L5. Ribosome component. | |
Ras suppressor protein 1 | RSU1 | Ras suppressor protein 1. Possibly involved in Ras-pathway signal transduction. | |
Malic enzyme 1 | ME1 | NADP-dependent Malic enzyme 1. Involved in lipids methabolsm. | |
Protein NOV homolog | NOV | Protein NOV homolog. Involved in a several cellular processes, including proliferation, adhesion, migration, differentiation, and surviving. | |
Ras-related protein Ral-A | RALA | Ras-related protein Ral-A. Multifunctional GTPase, involved in a several cellular processes, such as gene expression, cell migration, cell proliferation, oncogenic transformation, and membrane transport. | |
Arginyl-tRNA-protein transferase 1 | ATE1 | Arginyl-tRNA-protein transferase 1. Involved in posttranslational conjugation of arginine with protein N-terminal aspartate or glutamate in ubiquitin pathway degradation. | disputed status 3 |
Golgin subfamily A member 2 | GOLGA2 | Golgin subfamily A member 2. Peripherical membrane of Golgi apparatus. Involved in vesicle binding and membrane fusion. Plays a key role in Golgi apparatus desorption in mitosis. | |
Extended synaptotagmin-2 | ESYT2 | Extended synaptotagmin-2. Involved in EPR-cellular membrane contact generation. Plays key role in intracellular lipid transport and signal transduction. | Hypo-expressed 4 |
Myosin regulatory light chain 12A | MYL12A | Myosin regulatory light chain 12A. Myosin regulatory subunit, myosin subunit mediating contractile activity in both smooth muscle cells and nonmuscular cells. Participates in cytokinesis, receptor capping and cell migration | |
Tumor suppressor candidate 3 | TUSC3 | Tumor suppressor candidate 3. Supporting N-oligosaccharil transferase. | |
Insulin-degrading enzyme | IDE | Insulin-degrading enzyme. Involved in insulin, glucagon, bradykinin, and other peptide cellular degradation. Acts in intercellular signal transduction. | |
Myosin regulatory light polypeptide 9 | MYL9 | Myosin regulatory light polypeptide 9. Involved in cytokinesis, receptor capping, and cell migration. | |
Small nuclear ribonucleoprotein Sm D1 | SNRPD1 | Small nuclear ribonucleoprotein Sm D1. Plays important role in splicing. | |
U2 small nuclear RNA auxiliary factor 1 | U2AF1 | U2 small nuclear RNA auxiliary factor 1. Plays a key role in splicing. Mediates protein–protein and protein–RNA interactions. |
N (%) | ||
---|---|---|
Tumor stage | T1 | 21 (70%) |
T2 | 9 (30%) | |
Lymph node status | N0 | 24 (80%) |
N1 | 5 (17%) | |
N2 | 1 (6%) | |
Distant metastasis | M0 | 30 (100%) |
Receptor Status | ER-positive | 30 (100%) |
PR-positive | 30 (100%) | |
HER-2 Status | Negative | 30 (100%) |
Histologic Grade | II | 26 (87) |
III | 4 (13) | |
Histological type | Invasive ductal carcinoma | 30 (100%) |
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Tutanov, O.; Shefer, A.; Tsentalovich, Y.; Tamkovich, S. 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. Int. J. Mol. Sci. 2023, 24, 7279. https://doi.org/10.3390/ijms24087279
Tutanov O, Shefer A, Tsentalovich Y, Tamkovich S. 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. International Journal of Molecular Sciences. 2023; 24(8):7279. https://doi.org/10.3390/ijms24087279
Chicago/Turabian StyleTutanov, Oleg, Aleksei Shefer, Yuri Tsentalovich, and Svetlana Tamkovich. 2023. "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" International Journal of Molecular Sciences 24, no. 8: 7279. https://doi.org/10.3390/ijms24087279