miR-3113-5p, miR-223-3p, miR-133a-3p, and miR-499a-5p are sensitive biomarkers to diagnose sudden cardiac death.


Journal

Diagnostic pathology
ISSN: 1746-1596
Titre abrégé: Diagn Pathol
Pays: England
ID NLM: 101251558

Informations de publication

Date de publication:
31 Jul 2021
Historique:
received: 13 01 2021
accepted: 12 07 2021
entrez: 1 8 2021
pubmed: 2 8 2021
medline: 11 1 2022
Statut: epublish

Résumé

Sudden cardiac death (SCD) remains a great health threat and diagnostic challenge, especially those cases without positive autopsy findings. Molecular biomarkers have been urgently needed for the diagnosis of SCD displaying negative autopsy results. Due to their nature of stability, microRNAs (miRNAs) have emerged as promising diagnostic biomarkers for cardiovascular diseases. This study investigated whether specific cardio-miRNAs (miR-3113-5p, miR-223-3p, miR-499a-5p, and miR-133a-3p) could serve as potential biomarkers for the diagnosis of SCD. Thirty-four SCD cases were selected, 18 categorized as SCD with negative autopsy (SCD-negative autopsy) findings and 16 as SCD with positive autopsy (SCD-positive autopsy) findings such as coronary atherosclerosis and gross myocardial scar. Carbon monoxide (CO) intoxication (n = 14) and fatal injury death (n = 14) that displayed no pathological changes of myocardium were selected as control group, respectively. Histological analyses were performed to reveal the pathological changes and real-time quantitative polymerase chain reaction (RT-qPCR) was used to determine the expression of those miRNAs. It showed that heart samples from the SCD-negative autopsy group displayed no remarkable difference with regard to the expression of cleaved-caspase3, CD31, and CD68 and the extent of fibrotic tissue accumulation when compared with control samples. The four cardio-miRNAs were significantly up-regulated in the SCD samples as compared with control. When discriminating SCD from controls, receiver operating characteristic (ROC) curve analysis revealed that the areas under the curve (AUC) of these 4 miRNAs were from 0.7839 to 0.9043 with sensitivity of 64.71-97.06% and specificity of 70-100%. Moreover, when discriminating the specific causes of SCD, the four miRNA expressions increased in the heart from the SCD-negative autopsy group as relative to that from the SCD-positive autopsy group, and a combination of two miRNAs presented higher diagnostic value (AUC = 0.7407-0.8667). miR-3113-5p, miR-223-3p, miR-499a-5p, and miR-133a-3p may serve as independent diagnostic biomarkers for SCD, and a combination of two of these miRNAs could further discriminate detailed causes of SCD.

Sections du résumé

BACKGROUND BACKGROUND
Sudden cardiac death (SCD) remains a great health threat and diagnostic challenge, especially those cases without positive autopsy findings. Molecular biomarkers have been urgently needed for the diagnosis of SCD displaying negative autopsy results. Due to their nature of stability, microRNAs (miRNAs) have emerged as promising diagnostic biomarkers for cardiovascular diseases.
METHODS METHODS
This study investigated whether specific cardio-miRNAs (miR-3113-5p, miR-223-3p, miR-499a-5p, and miR-133a-3p) could serve as potential biomarkers for the diagnosis of SCD. Thirty-four SCD cases were selected, 18 categorized as SCD with negative autopsy (SCD-negative autopsy) findings and 16 as SCD with positive autopsy (SCD-positive autopsy) findings such as coronary atherosclerosis and gross myocardial scar. Carbon monoxide (CO) intoxication (n = 14) and fatal injury death (n = 14) that displayed no pathological changes of myocardium were selected as control group, respectively. Histological analyses were performed to reveal the pathological changes and real-time quantitative polymerase chain reaction (RT-qPCR) was used to determine the expression of those miRNAs.
RESULTS RESULTS
It showed that heart samples from the SCD-negative autopsy group displayed no remarkable difference with regard to the expression of cleaved-caspase3, CD31, and CD68 and the extent of fibrotic tissue accumulation when compared with control samples. The four cardio-miRNAs were significantly up-regulated in the SCD samples as compared with control. When discriminating SCD from controls, receiver operating characteristic (ROC) curve analysis revealed that the areas under the curve (AUC) of these 4 miRNAs were from 0.7839 to 0.9043 with sensitivity of 64.71-97.06% and specificity of 70-100%. Moreover, when discriminating the specific causes of SCD, the four miRNA expressions increased in the heart from the SCD-negative autopsy group as relative to that from the SCD-positive autopsy group, and a combination of two miRNAs presented higher diagnostic value (AUC = 0.7407-0.8667).
CONCLUSION CONCLUSIONS
miR-3113-5p, miR-223-3p, miR-499a-5p, and miR-133a-3p may serve as independent diagnostic biomarkers for SCD, and a combination of two of these miRNAs could further discriminate detailed causes of SCD.

Identifiants

pubmed: 34332589
doi: 10.1186/s13000-021-01127-x
pii: 10.1186/s13000-021-01127-x
pmc: PMC8325858
doi:

Substances chimiques

Biomarkers 0
MIRN133 microRNA, human 0
MIRN223 microRNA, human 0
MIRN3113 microRNA, human 0
MIRN499 microRNA, human 0
MicroRNAs 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

67

Subventions

Organisme : open project of Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases of Ministry of Education
ID : XN201810
Organisme : Research Project of Gannan Medical University
ID : XN201924 and YB201811
Organisme : Science and Technology Project of Jiangxi Provincial Department of Education
ID : GJJ160979 and GJJ180794
Organisme : open project of Key Laboratory of Forensic Pathology, Ministry of Public Security
ID : GAFYBL201903

Informations de copyright

© 2021. The Author(s).

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Auteurs

Fengping Yan (F)

Department of Forensic Medicine, School of Basic Medical Sciences, Gannan Medical University, 1 Yixueyuan Road, Zhanggong District, Ganzhou, Jiangxi, 341000, PR China. tomjiangxi@163.com.
Key Laboratory of Prevention and treatment of cardiovascular and cerebrovascular diseases of Ministry of Education, Gannan Medical University, 1 Yixueyuan Road, Zhanggong District, Ganzhou, Jiangxi, 341000, People's Republic of China. tomjiangxi@163.com.

Yuanyuan Chen (Y)

Department of Forensic Medicine, School of Basic Medical Sciences, Gannan Medical University, 1 Yixueyuan Road, Zhanggong District, Ganzhou, Jiangxi, 341000, PR China.
Key Laboratory of Prevention and treatment of cardiovascular and cerebrovascular diseases of Ministry of Education, Gannan Medical University, 1 Yixueyuan Road, Zhanggong District, Ganzhou, Jiangxi, 341000, People's Republic of China.

Xing Ye (X)

Department of Forensic Medicine, School of Basic Medical Sciences, Gannan Medical University, 1 Yixueyuan Road, Zhanggong District, Ganzhou, Jiangxi, 341000, PR China.
Key Laboratory of Prevention and treatment of cardiovascular and cerebrovascular diseases of Ministry of Education, Gannan Medical University, 1 Yixueyuan Road, Zhanggong District, Ganzhou, Jiangxi, 341000, People's Republic of China.

Fu Zhang (F)

Criminal Technology Center of Guangdong Province Public Security Bureau, Guangzhou, Guangdong, 510050, PR China.

Shiquan Wang (S)

Department of Forensic Medicine, School of Basic Medical Sciences, Gannan Medical University, 1 Yixueyuan Road, Zhanggong District, Ganzhou, Jiangxi, 341000, PR China.
Key Laboratory of Prevention and treatment of cardiovascular and cerebrovascular diseases of Ministry of Education, Gannan Medical University, 1 Yixueyuan Road, Zhanggong District, Ganzhou, Jiangxi, 341000, People's Republic of China.

Le Zhang (L)

Forensic Science Center of Gannan Medical University, 1 Yixueyuan Road, Zhanggong District, Ganzhou, Jiangxi, 341000, People's Republic of China.

Xiaoting Luo (X)

Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Gannan Medical University, 1 Yixueyuan Road, Zhanggong District, Ganzhou, Jiangxi, 341000, PR China. xtluo76@163.com.

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