Serum proteomic identification and validation of two novel atherosclerotic aortic aneurysm biomarkers, profilin 1 and complement factor D

Proteome Science

Research

Kengo Kusano¹  Tsukasa Osaki²  Hiroaki Yagi³  Hatsue Ishibashi-Ueda⁴  Hitoshi Matsuda⁵  Kenji Minatoya⁶  Yutaka Iba⁷  Yusuke Murakami⁸  Tsutomu Tomita⁹  Manabu Shirai^1,10  Masaki Wakabayashi^1,10  Cheol Son^1,11  Mitsuhiro Nishigori^1,12  Naoto Minamino^1,13 

[1] Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, 6-1 Kishibe-Shimmachi, 564-8565, Suita, Osaka, Japan;Department of Molecular Pharmacology, National Cerebral and Cardiovascular Center Research Institute, 6-1 Kishibe-Shimmachi, 564-8565, Suita, Osaka, Japan;Department of Biochemistry and Molecular Biology, Graduate School of Medical Science, Yamagata University, 2-2-2 Iidanishi, 990-9585, Yamagata, Japan;Department of Molecular Pharmacology, National Cerebral and Cardiovascular Center Research Institute, 6-1 Kishibe-Shimmachi, 564-8565, Suita, Osaka, Japan;FCM Business Development, HUP Business, Sysmex Corporation, 1-6-23 Goinoikemachi, Nagata-ku, 653-0851, Kobe, Japan;Department of Pathology, National Cerebral and Cardiovascular Center, 6-1 Kishibe-Shimmachi, 564-8565, Suita, Osaka, Japan;Department of Vascular Surgery, National Cerebral and Cardiovascular Center, 6-1 Kishibe-Shimmachi, 564-8565, Suita, Osaka, Japan;Department of Vascular Surgery, National Cerebral and Cardiovascular Center, 6-1 Kishibe-Shimmachi, 564-8565, Suita, Osaka, Japan;Department Cardiovascular Surgery, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawahara-cho, Sakyo-ku, 606-8507, Kyoto, Japan;Department of Vascular Surgery, National Cerebral and Cardiovascular Center, 6-1 Kishibe-Shimmachi, 564-8565, Suita, Osaka, Japan;Department Cardiovascular Surgery, Sapporo Medical University School of Medicine, 291 Nishi 16-chome Minami 1-jo, Chuo-ku, 060-8543, Sapporo, Japan;Fundamental Research Laboratory, Research and Development Division, Eiken Chemical Co., Ltd., 143 Nogi, Nogimachi, Shimotsuga-gun, 329-0114, Tochigi, Japan;Omics Research Center, National Cerebral and Cardiovascular Center, 6-1 Kishibe-Shimmachi, 564-8565, Suita, Osaka, Japan;National Cerebral and Cardiovascular Center Biobank, National Cerebral and Cardiovascular Center, 6-1 Kishibe-Shimmachi, 564-8565, Suita, Osaka, Japan;Omics Research Center, National Cerebral and Cardiovascular Center, 6-1 Kishibe-Shimmachi, 564-8565, Suita, Osaka, Japan;Omics Research Center, National Cerebral and Cardiovascular Center, 6-1 Kishibe-Shimmachi, 564-8565, Suita, Osaka, Japan;Department of Diabetes and Endocrinology, Kobe City Nishi-Kobe Medical Center, 5-7-1 Kojidai, Nishi-ku, 651-2273, Kobe, Japan;Omics Research Center, National Cerebral and Cardiovascular Center, 6-1 Kishibe-Shimmachi, 564-8565, Suita, Osaka, Japan;Department of Molecular Pharmacology, National Cerebral and Cardiovascular Center Research Institute, 6-1 Kishibe-Shimmachi, 564-8565, Suita, Osaka, Japan;Department of Chemistry, Faculty of Science, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, 814-0180, Fukuoka, Japan;Omics Research Center, National Cerebral and Cardiovascular Center, 6-1 Kishibe-Shimmachi, 564-8565, Suita, Osaka, Japan;Department of Molecular Pharmacology, National Cerebral and Cardiovascular Center Research Institute, 6-1 Kishibe-Shimmachi, 564-8565, Suita, Osaka, Japan;Present address: Department of Biochemistry, National Cerebral and Cardiovascular Center Research Institute, 6-1 Kishibe-Shimmachi, 564-8565, Suita, Osaka, Japan;

关键词: Aortic aneurysm;    Biomarker;    Proteome analysis;    Blood test;    Discovery;    Validation;   

DOI  :  10.1186/s12953-023-00212-x

 received in 2023-02-23, accepted in 2023-07-26,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundEffective diagnostic biomarkers for aortic aneurysm (AA) that are detectable in blood tests are required because early detection and rupture risk assessment of AA can provide insights into medical therapy and preventive treatments. However, known biomarkers for AA lack specificity and reliability for clinical diagnosis.MethodsWe performed proteome analysis of serum samples from patients with atherosclerotic thoracic AA (TAA) and healthy control (HC) subjects to identify diagnostic biomarkers for AA. Serum samples were separated into low-density lipoprotein, high-density lipoprotein, and protein fractions, and the major proteins were depleted. From the proteins identified in the three fractions, we narrowed down biomarker candidates to proteins uniformly altered in all fractions between patients with TAA and HC subjects and evaluated their capability to discriminate patients with TAA and those with abdominal AA (AAA) from HC subjects using receiver operating characteristic (ROC) analysis. For the clinical validation, serum concentrations of biomarker candidates were measured in patients with TAA and AAA registered in the biobank of the same institute, and their capability for the diagnosis was evaluated.ResultsProfilin 1 (PFN1) and complement factor D (CFD) showed the most contrasting profiles in all three fractions between patients with TAA and HC subjects and were selected as biomarker candidates. The PFN1 concentration decreased, whereas the CFD concentration increased in the sera of patients with TAA and AAA when compared with those of HC subjects. The ROC analysis showed that these proteins could discriminate patients with TAA and AAA from HC subjects. In the validation study, these candidates showed significant concentration differences between patients with TAA or AAA and controls. PFN1 and CFD showed sufficient area under the curve (AUC) in the ROC analysis, and their combination further increased the AUC. The serum concentrations of PFN1 and CFD also showed significant differences between patients with aortic dissection and controls in the validation study.ConclusionPFN1 and CFD are potential diagnostic biomarkers for TAA and AAA and measurable in blood samples; their diagnostic performance can be augmented by their combination. These biomarkers may facilitate the development of diagnostic systems to identify patients with AA.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

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