TY - JOUR
T1 - Utility of atherosclerosis-associated serum antibodies against colony-stimulating factor 2 in predicting the onset of acute ischemic stroke and prognosis of colorectal cancer
AU - Li, Shu Yang
AU - Yoshida, Yoichi
AU - Kubota, Masaaki
AU - Zhang, Bo Shi
AU - Matsutani, Tomoo
AU - Ito, Masaaki
AU - Yajima, Satoshi
AU - Yoshida, Kimihiko
AU - Mine, Seiichiro
AU - Machida, Toshio
AU - Hayashi, Aiko
AU - Takemoto, Minoru
AU - Yokote, Koutaro
AU - Ohno, Mikiko
AU - Nishi, Eiichiro
AU - Kitamura, Kenichiro
AU - Kamitsukasa, Ikuo
AU - Takizawa, Hirotaka
AU - Sata, Mizuki
AU - Yamagishi, Kazumasa
AU - Iso, Hiroyasu
AU - Sawada, Norie
AU - Tsugane, Shoichiro
AU - Iwase, Katsuro
AU - Shimada, Hideaki
AU - Iwadate, Yasuo
AU - Hiwasa, Takaki
N1 - Funding Information:
The authors would like to thank Masaki Takiguchi (Department of Biochemistry and Genetics, Graduate School of Medicine, Chiba University) for valuable discussions. We are grateful to Bert Vogelstein (Howard Hughes Medical Institute) and Mian Wu (University of Science and Technology of China) for providing expression and reporter plasmids.
Funding Information:
This work was supported, in part, by research grants from the Japan Science and Technology Agency (JST), JSPS KAKENHI Grant Number 20 K17953, 19 K09451, 17 K19810, 20 K07810, 16 K10520, 21 K08695, and 15 K10117. The Japan Public Health Center-based Prospective Study was supported by (National Cancer Center Research and Development Fund since 2011) and a Grant-in-Aid for Cancer Research from the Ministry of Health, Labour and Welfare of Japan (from 1989 to 2010).
Publisher Copyright:
Copyright © 2023 Li, Yoshida, Kubota, Zhang, Matsutani, Ito, Yajima, Yoshida, Mine, Machida, Hayashi, Takemoto, Yokote, Ohno, Nishi, Kitamura, Kamitsukasa, Takizawa, Sata, Yamagishi, Iso, Sawada, Tsugane, Iwase, Shimada, Iwadate and Hiwasa.
PY - 2023
Y1 - 2023
N2 - Introduction: Autoantibodies against inflammatory cytokines may be used for the prevention of atherosclerosis. Preclinical studies consider colony-stimulating factor 2 (CSF2) as an essential cytokine with a causal relationship to atherosclerosis and cancer. We examined the serum anti-CSF2 antibody levels in patients with atherosclerosis or solid cancer. Methods: We measured the serum anti-CSF2 antibody levels via amplified luminescent proximity homogeneous assay-linked immunosorbent assay based on the recognition of recombinant glutathione S-transferase-fused CSF2 protein or a CSF2-derived peptide as the antigen. Results: The serum anti-CSF2 antibody (s-CSF2-Ab) levels were significantly higher in patients with acute ischemic stroke (AIS), acute myocardial infarction (AMI), diabetes mellitus (DM), and chronic kidney disease (CKD) compared with healthy donors (HDs). In addition, the s-CSF2-Ab levels were associated with intima-media thickness and hypertension. The analyzes of samples obtained from a Japan Public Health Center-based prospective study suggested the utility of s-CSF2-Ab as a risk factor for AIS. Furthermore, the s-CSF2-Ab levels were higher in patients with esophageal, colorectal, gastric, and lung cancer than in HDs but not in those with mammary cancer. In addition, the s-CSF2-Ab levels were associated with unfavorable postoperative prognosis in colorectal cancer (CRC). In CRC, the s-CSF2-Ab levels were more closely associated with poor prognosis in patients with p53-Ab-negative CRC despite the lack of significant association of the anti-p53 antibody (p53-Ab) levels with the overall survival. Conclusion: S-CSF2-Ab was useful for the diagnosis of atherosclerosis-related AIS, AMI, DM, and CKD and could discriminate poor prognosis, especially in p53-Ab-negative CRC.
AB - Introduction: Autoantibodies against inflammatory cytokines may be used for the prevention of atherosclerosis. Preclinical studies consider colony-stimulating factor 2 (CSF2) as an essential cytokine with a causal relationship to atherosclerosis and cancer. We examined the serum anti-CSF2 antibody levels in patients with atherosclerosis or solid cancer. Methods: We measured the serum anti-CSF2 antibody levels via amplified luminescent proximity homogeneous assay-linked immunosorbent assay based on the recognition of recombinant glutathione S-transferase-fused CSF2 protein or a CSF2-derived peptide as the antigen. Results: The serum anti-CSF2 antibody (s-CSF2-Ab) levels were significantly higher in patients with acute ischemic stroke (AIS), acute myocardial infarction (AMI), diabetes mellitus (DM), and chronic kidney disease (CKD) compared with healthy donors (HDs). In addition, the s-CSF2-Ab levels were associated with intima-media thickness and hypertension. The analyzes of samples obtained from a Japan Public Health Center-based prospective study suggested the utility of s-CSF2-Ab as a risk factor for AIS. Furthermore, the s-CSF2-Ab levels were higher in patients with esophageal, colorectal, gastric, and lung cancer than in HDs but not in those with mammary cancer. In addition, the s-CSF2-Ab levels were associated with unfavorable postoperative prognosis in colorectal cancer (CRC). In CRC, the s-CSF2-Ab levels were more closely associated with poor prognosis in patients with p53-Ab-negative CRC despite the lack of significant association of the anti-p53 antibody (p53-Ab) levels with the overall survival. Conclusion: S-CSF2-Ab was useful for the diagnosis of atherosclerosis-related AIS, AMI, DM, and CKD and could discriminate poor prognosis, especially in p53-Ab-negative CRC.
KW - acute ischemic stroke
KW - antibody biomarker
KW - atherosclerosis
KW - colony-stimulating factor 2
KW - colorectal cancer
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U2 - 10.3389/fcvm.2023.1042272
DO - 10.3389/fcvm.2023.1042272
M3 - Article
AN - SCOPUS:85149416067
SN - 2297-055X
VL - 10
JO - Frontiers in Cardiovascular Medicine
JF - Frontiers in Cardiovascular Medicine
M1 - 1042272
ER -
