Detection of IDH1.R132H mutant protein in plasma extracellular vesicles and its application in preoperative noninvasive precision diagnosis of glioma.

PURPOSE: Development of a circulating extracellular vesicle-based IDH mutant protein detection technology for diagnosis of IDH mutation status in glioma, enabling personalized resection strategies, precision medication, and disease dynamics monitoring in IDH-mutant glioma. METHODS: We developed a tumor-classification strategy that discriminates tumor types by detecting the IDH1.R132H mutant protein in plasma extracellular vesicles using a bead-assisted, flow-cytometry–based assay. We assessed the differential expression’s capacity to distinguish tumor grades, analyzed pre-operative and post-operative expression variations, and verified consistency with histopathological immunohistochemistry. RESULTS: The method demonstrated a diagnostic sensitivity of 76.2% (95%CI: 54.9%–89.4%) and a specificity of 86.7% (95%CI: 62.1%–96.3%) for IDH-mutant glioma. Further analysis revealed that the expression level of the IDH mutant protein in plasma EVs was significantly associated with tumor grade in IDH-mutant glioma (P < 0.0001). Moreover, the expression level of the IDH mutant protein in plasma EVs significantly decreased in post-operative patients (P < 0.01) and showed a high degree of consistency with the pathological immunohistochemical results at different tumor grades. CONCLUSION: We propose a novel plasma extracellular-vesicle liquid biopsy with potential preoperative application in detecting IDH-mutant glioma, affording noninvasive, rapid, efficient, and low-cost assessment of IDH mutation status. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-026-15810-z.