TY - JOUR
T1 - Blood-based circulating microRNAs as diagnostic biomarkers for subclinical carotid atherosclerosis
T2 - A systematic review and meta-analysis with bioinformatics analysis
AU - Witarto, Bendix Samarta
AU - Visuddho, Visuddho
AU - Aldian, Fan Maitri
AU - Atmaja, Maxwell Salvador Surya
AU - Ariyanto, Melissa Valentina
AU - Witarto, Andro Pramana
AU - Wungu, Citrawati Dyah Kencono
AU - Susilo, Hendri
AU - Alsagaff, Mochamad Yusuf
AU - Rohman, Mohammad Saifur
N1 - Publisher Copyright:
© 2023 The Authors
PY - 2023/10
Y1 - 2023/10
N2 - Background: Atherosclerosis in carotid arteries can remain clinically undetected in its early development until an acute cerebrovascular event such as stroke emerges. Recently, microRNAs (miRNAs) circulating in blood have emerged as potential diagnostic biomarkers, but their performance in detecting subclinical carotid atherosclerosis has yet to be systematically researched. Aim: To investigate the diagnostic performance of circulating miRNAs in detecting subclinical carotid atherosclerosis. Methods: We systematically searched five electronic databases from inception to July 23, 2022. Subclinical carotid atherosclerosis was defined using carotid intima-media thickness (CIMT). Diagnostic accuracy parameters and correlation coefficients were pooled. A gene network visualisation and enrichment bioinformatics analysis were additionally conducted to search for potential target genes and pathway regulations of the miRNAs. Results: Fifteen studies (15 unique miRNAs) comprising 2542 subjects were identified. Circulating miRNAs had a pooled sensitivity of 85% (95% CI 80%–89%), specificity of 84% (95% CI 78%–88%), positive likelihood ratio of 5.19 (95% CI 3.97–6.80), negative likelihood ratio of 0.18 (95% CI 0.13–0.23), diagnostic odds ratio of 29.48 (95% CI 21.15–41.11), and area under the summary receiver operating characteristic curve of 0.91 (95% CI 0.88–0.93), with a strong correlation to CIMT (pooled coefficient 0.701; 95% CI 0.664–0.731). Bioinformatics analysis revealed a major role of the miRNAs, as shown by their relation with CCND1, KCTD15, SPARC, WWTR1, VEGFA genes, and multiple pathways involved in the pathogenesis of carotid atherosclerosis. Conclusion: Circulating miRNAs had excellent accuracy in detecting subclinical carotid atherosclerosis, suggesting their utilisation as novel diagnostic tools.
AB - Background: Atherosclerosis in carotid arteries can remain clinically undetected in its early development until an acute cerebrovascular event such as stroke emerges. Recently, microRNAs (miRNAs) circulating in blood have emerged as potential diagnostic biomarkers, but their performance in detecting subclinical carotid atherosclerosis has yet to be systematically researched. Aim: To investigate the diagnostic performance of circulating miRNAs in detecting subclinical carotid atherosclerosis. Methods: We systematically searched five electronic databases from inception to July 23, 2022. Subclinical carotid atherosclerosis was defined using carotid intima-media thickness (CIMT). Diagnostic accuracy parameters and correlation coefficients were pooled. A gene network visualisation and enrichment bioinformatics analysis were additionally conducted to search for potential target genes and pathway regulations of the miRNAs. Results: Fifteen studies (15 unique miRNAs) comprising 2542 subjects were identified. Circulating miRNAs had a pooled sensitivity of 85% (95% CI 80%–89%), specificity of 84% (95% CI 78%–88%), positive likelihood ratio of 5.19 (95% CI 3.97–6.80), negative likelihood ratio of 0.18 (95% CI 0.13–0.23), diagnostic odds ratio of 29.48 (95% CI 21.15–41.11), and area under the summary receiver operating characteristic curve of 0.91 (95% CI 0.88–0.93), with a strong correlation to CIMT (pooled coefficient 0.701; 95% CI 0.664–0.731). Bioinformatics analysis revealed a major role of the miRNAs, as shown by their relation with CCND1, KCTD15, SPARC, WWTR1, VEGFA genes, and multiple pathways involved in the pathogenesis of carotid atherosclerosis. Conclusion: Circulating miRNAs had excellent accuracy in detecting subclinical carotid atherosclerosis, suggesting their utilisation as novel diagnostic tools.
KW - Biomarkers
KW - Cardiovascular disease
KW - Carotid intima-media thickness
KW - Diagnosis
KW - MicroRNAs
KW - Subclinical carotid atherosclerosis
UR - http://www.scopus.com/inward/record.url?scp=85171559098&partnerID=8YFLogxK
U2 - 10.1016/j.dsx.2023.102860
DO - 10.1016/j.dsx.2023.102860
M3 - Review article
AN - SCOPUS:85171559098
SN - 1871-4021
VL - 17
JO - Diabetes and Metabolic Syndrome: Clinical Research and Reviews
JF - Diabetes and Metabolic Syndrome: Clinical Research and Reviews
IS - 10
M1 - 102860
ER -