Use of a panel of four microRNAs in CSF as a predicted biomarker for postoperative neoangiogenesis in moyamoya disease

Abstract

Introduction and Aims At present, the treatment for moyamoya disease (MMD) primarily consists of combined direct and indirect bypass surgery. Nevertheless, more than half of indirect bypass surgeries fail to develop good collaterals from the dura and temporal muscle. This study aimed to investigate whether microRNAs (miRNAs) in cerebrospinal fluid (CSF) could serve as biomarkers for the prediction of postoperative collateral formation. Methods Moyamoya disease patients with indirect bypass surgery were divided into angiogenesis and non‐angiogenesis groups, CSF was obtained, and miRNA sequencing was performed using the CSF. Candidate miRNAs were filtered and subsequently verified through qRT‐PCR. The diagnostic utility of these differential miRNAs was investigated by using receiver operating characteristic (ROC) curve analysis. Finally, the potential biological processes and signaling pathways associated with candidate miRNAs were analyzed using R software. Results The expression levels of four miRNAs (miR‐92a‐3p, miR‐486‐3p, miR‐25‐3p, and miR‐155‐5p) were significantly increased in the angiogenesis group. By combining these four miRNAs (area under the curve [AUC] =0.970), we established an accurate predictive model of collateral circulation after indirect bypass surgery in MMD patients. GO and KEGG analyses demonstrated a high correlation with biological processes and signaling pathways related to angiogenesis. Conclusion The 4‐miRNA signature is a good model to predict angiogenesis after indirect bypass surgery and help the surgeon to select a appreciate bypass strategy.

TGFβ1 as a Predictive Biomarker for Collateral Formation Within Ischemic Moyamoya Disease

“…In previous studies, the spontaneous transdural collaterals that appear were considered the brain's ability to promote angiogenesis and served as a radiographic biomarker to predict the collaterals' development after revascularization ( 7 , 8 , 12 ). In this research, we detected that the levels of TGFβ1 were associated with the formation of transdural collaterals, indicating that TGFβ1 may become a vital biomarker in predicting collaterals after revascularization.…”

“…Bypass surgery is recommended as a first-line treatment of MMD, including direct bypass, indirect bypass, and combined strategies (8)(9)(10). Moreover, direct bypass surgery can immediately increase blood flow, but indirect bypass requires more time to produce angiogenesis from the muscle and dura (8,9).…”

“…Bypass surgery is recommended as a first-line treatment of MMD, including direct bypass, indirect bypass, and combined strategies (8)(9)(10). Moreover, direct bypass surgery can immediately increase blood flow, but indirect bypass requires more time to produce angiogenesis from the muscle and dura (8,9). Also, there is a lack of effective collateral angiogenesis needed to prevent strokes after indirect bypass surgery immediately (11).…”

“…Therefore, a comprehensive understanding of the relevant mechanism of preoperative collateral development is expected to guide the establishment of good postoperative collateral. However, the molecular mechanisms regulating angiogenesis in the progression of collateral remain unclear and lack a reliable biomarker to predict the collateral (8,(13)(14)(15).…”

RNA profiling of sEV (small extracellular vesicles)/exosomes reveals biomarkers and vascular endothelial dysplasia with moyamoya disease

“…15 Wang et al identified a novel and highly sensitive e-miRNA signature for MMD detection and explored potential targets. 16 However, differences in exosomal RNAs between patients with MMD, ICAD, and healthy controls, as well as how they affect the pathogenesis of MMD and ICAD, remain unknown.…”