Bioinformatics Analysis of ZDHHC-protein Acyltransferase for Predicting the Rupture of Aneurysmal Subarachnoid...

Intracranial aneurysms (IAs) can cause life-threatening subarachnoid hemorrhage upon rupture, yet their molecular mechanisms remain poorly understood. Proteins encoded by the ZDHHC genes mediate protein palmitoylation and are involved in brain injury processes, but their relationship with IA rupture is unclear.

This study utilized gene expression profiles from the Gene Expression Omnibus (GEO) database for unruptured intracranial aneurysms (UIAs) and ruptured intracranial aneurysms (RIAs) using two-tailed Student's t-test, and univariate and multivariate logistic regression analyses. A predictive risk model and nomogram for IA rupture were constructed using machine learning methods, and the model's accuracy was evaluated with calibration curves, C-index, clinical decision curves, and clinical impact curves. Receiver operating characteristic (ROC) curves demonstrated good diagnostic performance in both training and validation datasets. Additionally, a rat SAH model was used to validate the increased expression of the six ZDHHC-encoded proteins post-SAH via Western blotting.

Six high-risk genes associated with IA rupture were identified: ZDHHC3, ZDHHC5, ZDHHC7, ZDHHC8, ZDHHC9, and ZDHHC13.

ZDHHC family genes can serve as potential biomarkers for IA rupture, but their relationship with prognosis still needs further investigation.

ZDHHC family genes can predict IA rupture and hold promise as clinical biomarkers, which also suggests the critical role of palmitoylation modification in the pathological process of SAH.