Increased plasma levels of circPTP4A2 and circTLK2 are associated with stroke injury

Xingzhi Wang; Shenyang Zhang; Zuohui Zhang; Jie Zu; Hongjuan Shi; Lu Yu; Bingchen Lv; Likun Cui; Wenqi Mao; Di Wu; Guiyun Cui

doi:10.1002/acn3.51837

Increased plasma levels of circPTP4A2 and circTLK2 are associated with stroke injury

Ann Clin Transl Neurol. 2023 Aug;10(8):1481-1492. doi: 10.1002/acn3.51837. Epub 2023 Jun 23.

Authors

Xingzhi Wang^#^{1

2

3}, Shenyang Zhang^#^{1

3

4}, Zuohui Zhang^{1

3}, Jie Zu^{1

3}, Hongjuan Shi^{1

3}, Lu Yu^{1

3}, Bingchen Lv^{1

3}, Likun Cui^{1

3}, Wenqi Mao^{1

3}, Di Wu^{1

3}, Guiyun Cui^{1

3}

Affiliations

¹ Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
² Jiangsu Key Laboratory of Brain Disease and Bioinformation, Research Center for Biochemistry and Molecular Biology, Xuzhou Medical University, Xuzhou, Jiangsu, China.
³ Institute of Stroke Research, Xuzhou Medical University, Xuzhou, Jiangsu, China.
⁴ School of Medicine, Southeast University, Nanjing, Jiangsu, China.

^# Contributed equally.

Abstract

Objective: Accumulating studies have shown that circulating circular RNAs (circRNAs) represent novel biomarkers for many human diseases. We investigated whether plasma circPTP4A2 and circTLK2 levels are associated with stroke severity, infarct volume, stroke etiology, and functional outcome in acute ischemic stroke (AIS) patients.

Methods: We applied quantitative real-time PCR (qPCR) to measure plasma circPTP4A2 and circTLK2 levels of 236 AIS patients within 72 h of symptoms onset and 136 healthy controls. We further assessed the National Institutes of Health Stroke Scale (NIHSS), infarct size, the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification and the 90-day modified Rankin scale (mRS) for each patient.

Results: At admission, plasma circPTP4A2 and circTLK2 levels in patients with moderate to severe stroke were significantly higher compared to those with mild stroke. Logistic regression and receiver-operating characteristic (ROC) curve analyses indicated that they might function as predictive biomarkers for moderate to severe stroke. We also observed a medium positive correlation between these two circRNAs and NIHSS. Plasma circPTP4A2 and circTLK2 levels were slight positively correlated with cerebral infarct volume only in anterior circulation infarction (ACI) patients. Levels of both circPTP4A2 and circTLK2 were closely related with large artery atherosclerosis (LAA) stroke. Moreover, changes within 7 days after admission in circPTP4A2 and circTLK2 were able to predict unfavorable clinical outcome 90 days after AIS.

Interpretation: These results demonstrate that plasma circPTP4A2 and circTLK2 strongly correlated with severity, subtypes and prognosis of AIS, and they could serve as promising biomarkers.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers
Humans
Infarction / complications
Ischemic Stroke* / complications
RNA, Circular / genetics
Stroke* / diagnosis
United States

Substances

RNA, Circular
Biomarkers

Grants and funding

This work was funded by Key R&D Program (Social Development) of Jiangsu Province grant BE2021630; National Natural Science Foundation of China grant 82171305; Science and Technology Project of Xuzhou Health Commission grant XWKYHT20220156; the Open Project of Key Laboratory of Colleges and Universities in Jiangsu Province grant XZSYSKF2022021; the Science and Technology Project of Xuzhou City grants KC19131 and KC20113.