Plasma Desmoplakin as a Novel Biomarker for Early-Onset Susceptibility and Prognostic Stratification in Young Intracerebral Hemorrhage

OBJECTIVE: This study aimed to identify plasma protein biomarkers associated with the presence and prognosis of intracerebral hemorrhage (ICH) in young adults. METHODS: We conducted a plasma proteomic analysis to identify differential proteins (DEPs) in an exploratory cohort, consisting of young spontaneous intracerebral hemorrhage patients (YSICH, N=24), and a control group (N=26: Cranial trauma patients, CT-Ctrl n=15; Brain tumor patients, BT-Ctrl n=11). Potential biomarker was then selected from these differential proteins based on fold change(FC), machine learning algorithms and previous studies. The level of this biomarker was validated using ELISA kits in an independent validation cohort, consisting of young spontaneous intracerebral hemorrhage patients (YSICH, N=144), and geriatric spontaneous intracerebral hemorrhage patients (GEICH, N=144). RESULTS: Within the exploratory cohort, 112 DEPs were significantly associated with YSICH and Desmoplakin (DSP) emerged as a key biomarker (p=0.007, FC=0.434). In the validation cohort, plasma DSP levels in young patients were significantly lower than in elderly patients (p < 0.001), demonstrating good discriminative ability for early-onset ICH susceptibility (AUC = 0.805, 95% CI: 0.750 to 0.861). Moreover, combining DSP with the ICH score improved prognostic accuracy, with the AUC value increasing from 0.795 to 0.828 (ΔAUC = 0.034), compared to using the ICH score alone. Notably, subgroup analysis revealed that this prognostic utility was highly specific to young patients presenting with mild-to-moderate clinical severity. CONCLUSION: Reduced plasma DSP levels reflect a susceptibility to early-onset ICH. Furthermore, DSP represents a promising adjunctive biomarker for prognostic risk stratification, particularly in young patients with mild-to-moderate disease severity.