Authors (including presenting author) :
Qianyun Li (1), Xiaodan Zhang (1), Yilin Zhang (1), Rex Pui Kin Lam (1), Weinv Fan (2), Yulan Jin (3), Chengcheng Ji (4), Jonathan Johnson (5), Timothy Hudson Rainer (1)
Affiliation :
(1) Department of Emergency Medicine, The University of Hong Kong, Hong Kong SAR, China
(2) Department of Neurology, Ningbo No.2 Hospital, Ningbo, Zhejiang Province, China
(3) Department of Clinical Laboratory, Ningbo No.2 Hospital, Ningbo, Zhejiang Province, China
(4) School of Medicine, Shaoxing University, Shaoxing, Zhejiang Province, China
(5) School of Humanities, the University of Hong Kong, Hong Kong SAR, China
Introduction :
Current guidelines recommend intravenous thrombolysis (IVT) for acute ischaemic stroke (AIS) patients within 4.5 hours of symptom onset. Those with an unknown onset time are generally ineligible for such therapy.
Objectives :
Our study aimed to use proteomic biomarkers to identify AIS patients with a stroke onset time within 4.5 hours when the history was not clear.
Methodology :
We conducted a retrospective case-control study between June 2022 and July 2023 in Ningbo No. 2 Hospital, recruiting 30 AIS patients (mean age 70.6 years, 76.7% male) and 12 controls (mean age 66.2 years, 58.3% male). Patients with AIS were grouped into early-onset (ES, symptom onset time ≤ 4.5 hours, n = 16) and late-onset (LS, symptom onset 4.5–24 hours, n = 14). Plasma proteins were identified using 4-dimentional-data-independent acquisition–based liquid chromatography–mass spectrometry. A stepwise analysis, including receiver operating characteristic curves, nonlinear regression, and machine learning, was conducted to screen for candidate proteins with optimal performance in discriminating ES and LS. Multiple logistic regression was used to construct various combinations using the selected proteins.
Result & Outcome :
Of 950 credible proteins, six discriminated ES from LS, with the area under curve (AUC) ranging from 0.897 to 0.951; protein 4.2 (EPB42) achieved the highest AUC of 0.951 (95% confidence interval [CI] 0.882–1), a specificity of 0.929 (95% CI 0.714–1) and a sensitivity of 0.875 (95% CI 0.750–1). Ten combinations were derived from these six proteins, of which EPB42 and phosphatidylethanolamine-binding protein 1 achieved an AUC of 0.991 (95% CI 0.970–1), a specificity of 0.929 (95% CI 0.857–1), and a sensitivity of 1 (95% CI 0.875–1) in differentiating ES from LS.
