Transcriptome-Based Dissection of Intracranial Aneurysms Unveils an "Immuno-Thermal" Microenvironment and Defines a...

Immune inflammation plays an essential role in the formation and rupture of intracranial aneurysm (IA). However, the current limited knowledge of alterations in the immune microenvironment of IA has hampered the mastery of pathological mechanisms and technological advances, such as molecular diagnostic and coated stent-based molecular therapy. In this study, seven IA datasets were enrolled from the GEO database to decode the immune microenvironment and relevant biometric alterations. The ssGSEA algorithm was employed for immune infiltration assessment. IAs displayed abundant immune cell infiltration, activated immune-related pathways, and high expression of immune-related genes. Several immunosuppression cells and genes were also coordinately upregulated in IAs. Five immune-related hub genes, including CXCL10, IL6, IL10, STAT1, and VEGFA, were identified from the protein-protein interaction network and further detected at the protein level. CeRNA networks and latent drugs targeting the hub genes were predicted for targeted therapy reference. Two gene modules recognized via WCGNA were functionally associated with contractile smooth muscle loss and extracellular matrix metabolism, respectively. In blood datasets, a pathological feature-derived gene signature (PFDGS) for IA diagnosis and rupture risk prediction was established using machine learning. Patients with high PFDGS scores may possess adverse biological alterations and present with a high risk of morbidity or IA rupture, requiring more vigilance or prompt intervention. Overall, we systematically unveiled an "immuno-thermal" microenvironment characterized by co-enhanced immune activation and immunosuppression in IA, which provides a novel insight into molecular pathology. The PFDGS is a promising signature for optimizing risk surveillance and clinical decision-making in IA patients.