PMID- 38138918 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20231225 IS - 2075-4426 (Print) IS - 2075-4426 (Electronic) IS - 2075-4426 (Linking) VI - 13 IP - 12 DP - 2023 Dec 5 TI - Blood Plasma Circulating DNA-Protein Complexes: Involvement in Carcinogenesis and Prospects for Liquid Biopsy of Breast Cancer. LID - 10.3390/jpm13121691 [doi] LID - 1691 AB - 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. FAU - Shefer, Aleksei AU - Shefer A AUID- ORCID: 0000-0001-5369-397X AD - V. Zelman Institute for Medicine and Psychology, Novosibirsk State University, 630090 Novosibirsk, Russia. FAU - Tutanov, Oleg AU - Tutanov O AD - Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37203, USA. FAU - Belenikin, Maxim AU - Belenikin M AD - Evogen LLC, 115191 Moscow, Russia. FAU - Tsentalovich, Yuri P AU - Tsentalovich YP AUID- ORCID: 0000-0002-1380-3000 AD - International Tomography Center, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia. FAU - Tamkovich, Svetlana AU - Tamkovich S AUID- ORCID: 0000-0001-7774-943X AD - V. Zelman Institute for Medicine and Psychology, Novosibirsk State University, 630090 Novosibirsk, Russia. LA - eng GR - 22-25-00130/Russian Science Foundation/ PT - Journal Article DEP - 20231205 PL - Switzerland TA - J Pers Med JT - Journal of personalized medicine JID - 101602269 PMC - PMC10744380 OTO - NOTNLM OT - MALDI-TOF mass spectrometry OT - bioinformatics analysis OT - breast cancer OT - circulating DNA OT - liquid biopsy OT - nucleoprotein complexes OT - plasma COIS- Dr. Maxim Belenikin is an employee of Evogen LLC. He was engaged in analyzing proteins on Gene ontology term (GO). This analytical work is in no way related to the company he works for. EDAT- 2023/12/23 12:43 MHDA- 2023/12/23 12:44 PMCR- 2023/12/05 CRDT- 2023/12/23 01:19 PHST- 2023/10/12 00:00 [received] PHST- 2023/11/21 00:00 [revised] PHST- 2023/11/29 00:00 [accepted] PHST- 2023/12/23 12:44 [medline] PHST- 2023/12/23 12:43 [pubmed] PHST- 2023/12/23 01:19 [entrez] PHST- 2023/12/05 00:00 [pmc-release] AID - jpm13121691 [pii] AID - jpm-13-01691 [pii] AID - 10.3390/jpm13121691 [doi] PST - epublish SO - J Pers Med. 2023 Dec 5;13(12):1691. doi: 10.3390/jpm13121691.