Absolute Quantitative Targeted Monitoring of Potential Plasma Protein Biomarkers: A Pilot Study on Healthy Individuals

Background/Objectives: The development of blood tests for the early detection of individual predisposition to socially significant diseases remains a pressing issue. Methods: In this pilot study, multiple reaction monitoring mass spectrometry (MRM-MS) with a BAK-270 assay was applied for protein con...

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Main Authors: Alexey S. Kononikhin, Natalia L. Starodubtseva, Alexander G. Brzhozovskiy, Alisa O. Tokareva, Daria N. Kashirina, Natalia V. Zakharova, Anna E. Bugrova, Maria I. Indeykina, Liudmila Kh. Pastushkova, Irina M. Larina, Vladimir A. Mitkevich, Alexander A. Makarov, Evgeny N. Nikolaev
Format: Article
Language:English
Published: MDPI AG 2024-10-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/12/10/2403
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author Alexey S. Kononikhin
Natalia L. Starodubtseva
Alexander G. Brzhozovskiy
Alisa O. Tokareva
Daria N. Kashirina
Natalia V. Zakharova
Anna E. Bugrova
Maria I. Indeykina
Liudmila Kh. Pastushkova
Irina M. Larina
Vladimir A. Mitkevich
Alexander A. Makarov
Evgeny N. Nikolaev
author_facet Alexey S. Kononikhin
Natalia L. Starodubtseva
Alexander G. Brzhozovskiy
Alisa O. Tokareva
Daria N. Kashirina
Natalia V. Zakharova
Anna E. Bugrova
Maria I. Indeykina
Liudmila Kh. Pastushkova
Irina M. Larina
Vladimir A. Mitkevich
Alexander A. Makarov
Evgeny N. Nikolaev
author_sort Alexey S. Kononikhin
collection DOAJ
description Background/Objectives: The development of blood tests for the early detection of individual predisposition to socially significant diseases remains a pressing issue. Methods: In this pilot study, multiple reaction monitoring mass spectrometry (MRM-MS) with a BAK-270 assay was applied for protein concentrations analysis in blood plasma from 21 healthy volunteers of the European cohort. Results: The levels of 138 plasma proteins were reliably and precisely quantified in no less than 50% of samples. The quantified proteins included 66 FDA-approved markers of cardiovascular diseases (CVD), and other potential biomarkers of pathologies such as cancer, diabetes mellitus, and Alzheimer’s disease. The analysis of individual variations of the plasma proteins revealed significant differences between the male (11) and female (10) groups. In total, fifteen proteins had a significantly different concentration in plasma; this included four proteins that exhibited changes greater than ±1.5-fold, three proteins (RBP4, APCS, and TTR) with higher levels in males, and one (SHBG) elevated in females. The obtained results demonstrated considerable agreement with the data collected from 20 samples of a North American cohort, which were analyzed with the similar MRM assay. The most significant differences between the cohorts of the two continents were observed in the level of 42 plasma proteins (including 24 FDA markers), of which 17 proteins showed a ≥1.5-fold change, and included proteins increased in North Americans (APOB, CRTAC1, C1QB, C1QC, C9, CRP, HP, IGHG1, IGKV4-1, SERPING1, RBP4, and AZGP1), as well as those elevated in Europeans (APOF, CD5L, HBG2, SELPLG, and TNA). Conclusions: The results suggest a different contribution of specific (patho)physiological pathways (e.g., immune system and blood coagulation) to the development of socially significant diseases in Europeans and North Americans, and they should be taken into account when refining diagnostic panels.
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spelling doaj-art-2a40bf520acd4d018a20eac60e8220632025-08-20T02:10:57ZengMDPI AGBiomedicines2227-90592024-10-011210240310.3390/biomedicines12102403Absolute Quantitative Targeted Monitoring of Potential Plasma Protein Biomarkers: A Pilot Study on Healthy IndividualsAlexey S. Kononikhin0Natalia L. Starodubtseva1Alexander G. Brzhozovskiy2Alisa O. Tokareva3Daria N. Kashirina4Natalia V. Zakharova5Anna E. Bugrova6Maria I. Indeykina7Liudmila Kh. Pastushkova8Irina M. Larina9Vladimir A. Mitkevich10Alexander A. Makarov11Evgeny N. Nikolaev12Project Center of Advanced Mass Spectrometry Technologies, 121205 Moscow, RussiaV.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia, 117997 Moscow, RussiaProject Center of Advanced Mass Spectrometry Technologies, 121205 Moscow, RussiaV.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia, 117997 Moscow, RussiaInstitute of Biomedical Problems, Russian Federation State Scientific Research Center, Russian Academy of Sciences, 123007 Moscow, RussiaEmanuel Institute of Biochemical Physics, Russian Academy of Sciences, 119334 Moscow, RussiaV.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia, 117997 Moscow, RussiaEmanuel Institute of Biochemical Physics, Russian Academy of Sciences, 119334 Moscow, RussiaInstitute of Biomedical Problems, Russian Federation State Scientific Research Center, Russian Academy of Sciences, 123007 Moscow, RussiaInstitute of Biomedical Problems, Russian Federation State Scientific Research Center, Russian Academy of Sciences, 123007 Moscow, RussiaEngelhardt Institute of Molecular Biology, Russian Academy of Science, 119991 Moscow, RussiaEngelhardt Institute of Molecular Biology, Russian Academy of Science, 119991 Moscow, RussiaProject Center of Advanced Mass Spectrometry Technologies, 121205 Moscow, RussiaBackground/Objectives: The development of blood tests for the early detection of individual predisposition to socially significant diseases remains a pressing issue. Methods: In this pilot study, multiple reaction monitoring mass spectrometry (MRM-MS) with a BAK-270 assay was applied for protein concentrations analysis in blood plasma from 21 healthy volunteers of the European cohort. Results: The levels of 138 plasma proteins were reliably and precisely quantified in no less than 50% of samples. The quantified proteins included 66 FDA-approved markers of cardiovascular diseases (CVD), and other potential biomarkers of pathologies such as cancer, diabetes mellitus, and Alzheimer’s disease. The analysis of individual variations of the plasma proteins revealed significant differences between the male (11) and female (10) groups. In total, fifteen proteins had a significantly different concentration in plasma; this included four proteins that exhibited changes greater than ±1.5-fold, three proteins (RBP4, APCS, and TTR) with higher levels in males, and one (SHBG) elevated in females. The obtained results demonstrated considerable agreement with the data collected from 20 samples of a North American cohort, which were analyzed with the similar MRM assay. The most significant differences between the cohorts of the two continents were observed in the level of 42 plasma proteins (including 24 FDA markers), of which 17 proteins showed a ≥1.5-fold change, and included proteins increased in North Americans (APOB, CRTAC1, C1QB, C1QC, C9, CRP, HP, IGHG1, IGKV4-1, SERPING1, RBP4, and AZGP1), as well as those elevated in Europeans (APOF, CD5L, HBG2, SELPLG, and TNA). Conclusions: The results suggest a different contribution of specific (patho)physiological pathways (e.g., immune system and blood coagulation) to the development of socially significant diseases in Europeans and North Americans, and they should be taken into account when refining diagnostic panels.https://www.mdpi.com/2227-9059/12/10/2403proteomicsbloodplasmahealthy volunteersbiomarkersMRM
spellingShingle Alexey S. Kononikhin
Natalia L. Starodubtseva
Alexander G. Brzhozovskiy
Alisa O. Tokareva
Daria N. Kashirina
Natalia V. Zakharova
Anna E. Bugrova
Maria I. Indeykina
Liudmila Kh. Pastushkova
Irina M. Larina
Vladimir A. Mitkevich
Alexander A. Makarov
Evgeny N. Nikolaev
Absolute Quantitative Targeted Monitoring of Potential Plasma Protein Biomarkers: A Pilot Study on Healthy Individuals
Biomedicines
proteomics
blood
plasma
healthy volunteers
biomarkers
MRM
title Absolute Quantitative Targeted Monitoring of Potential Plasma Protein Biomarkers: A Pilot Study on Healthy Individuals
title_full Absolute Quantitative Targeted Monitoring of Potential Plasma Protein Biomarkers: A Pilot Study on Healthy Individuals
title_fullStr Absolute Quantitative Targeted Monitoring of Potential Plasma Protein Biomarkers: A Pilot Study on Healthy Individuals
title_full_unstemmed Absolute Quantitative Targeted Monitoring of Potential Plasma Protein Biomarkers: A Pilot Study on Healthy Individuals
title_short Absolute Quantitative Targeted Monitoring of Potential Plasma Protein Biomarkers: A Pilot Study on Healthy Individuals
title_sort absolute quantitative targeted monitoring of potential plasma protein biomarkers a pilot study on healthy individuals
topic proteomics
blood
plasma
healthy volunteers
biomarkers
MRM
url https://www.mdpi.com/2227-9059/12/10/2403
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