Differentially Expressed Genes and Biological Pathways in Moyamoya Disease: A Systematic Review and Meta-analysis of Transcriptomic Studies.

Moyamoya disease (MMD) is a chronic cerebrovascular disorder characterised by the progressive stenosis of bilateral internal carotid arteries, predominantly affecting East Asian populations. Recent advances in RNA expression studies have provided insights into the molecular underpinnings of MMD. This study aims to aggregate transcriptomic data to identify the top differentially expressed genes (DEGs) across published studies and elucidate biological pathways associated with MMD. We conducted a systematic search of the PubMed and Embase databases, identifying 15 transcriptomic studies involving RNA transcriptome-wide analyses of 177 MMD patients. Following preprocessing of significantly upregulated and downregulated Genes, we performed biological pathway enrichment analysis to identify DEGs between MMD patients and control. Additionally, Gene-transcription factor and Gene-drug interaction analyses were conducted to explore potential therapeutic repurposing. Our analysis revealed 98 upregulated and 37 downregulated DEGs (Bonferroni-adjusted p-values < 0.05) significantly associated with MMD. In peripheral blood cells (PBCs), upregulated pathways were predominantly associated with mitotic kinetochore assembly and response to axon injury, while downregulated pathways were linked to cellular response to brain-derived neurotrophic factor (BDNF) and extracellular matrix organization. In vascular tissues, mitotic pathways were notably upregulated, whereas the regulation of cell proliferation and blood circulation pathways were suppressed. Gene-drug interaction analysis highlighted MI-773 and MLN 8237 as potential MMD therapy. This study identifies distinct biological pathways that are dysregulated in key tissues of MMD patients. Given the current limited treatment options for MMD, our findings offer potential biomarkers for risk stratification and novel therapeutic targets that could pave the way for improved management of this debilitating disease.