胶质母细胞瘤组织力学特征的空间异质性及其与细胞外基质重塑的多层级关联研究OA

Objective To investigate the relationship among tissue mechanics,spatial heterogeneity,and extracellular matrix(ECM)remodeling during glioblastoma(GBM)recurrence.Methods Tissue specimens from 20 primary GBM and 17 recurrent GBM cases were collected.Tissue mechanical properties were measured using AFM.Young's modulus was calculated based on the Hertz contact model.Mechanical differences between the tumor core and margin were compared.ECM molecule expression was detected,correlations between tissue stiffness and ECM remodeling were analyzed,and unbiased proteomic analysis was performed in paired samples.Results Young's modulus increased with WHO grade and was significantly higher in recurrent GBM than in primary GBM(P<0.05).Recurrent GBM showed a stiffness gradient with the core stiffer than the margin,whereas primary GBM displayed the opposite pattern.ECM molecule expression was increased in recurrent GBM and positively correlated with tissue stiffness.Cellular composition-related markers showed no consistent changes,suggesting that mechanical reinforcement was mainly associated with ECM remodeling.Proteomic analysis further revealed enrichment of differential proteins in ECM-related biological processes and signaling pathways.Conclusions GBM recurrence is accompanied by tissue mechanical reinforcement and spatially heterogeneous ECM remodeling,suggesting that coordinated stiffness-matrix remodeling may represent an important feature of recurrent microenvironmental evolution.