Integrated analysis of amide proton transfer weighted MRI and proteomics uncovers altered protein dynamics in...

Elevated amide proton transfer-weighted (APTw) MRI signals in glioblastoma (GBM) are often linked to increased intracellular mobile proteins, but the associated molecular patterns in human tissue remain unclear. We examined the relationship between regional APTw features and cellular protein composition and profiled proteomic differences between tumor and peritumoral tissue.

In this single-center prospective study, preoperative MRI data were integrated with intraoperative neuronavigation for 12 image-guided tissue samples (8 tumor and 4 peritumoral). Total, cytoplasmic, and nuclear proteins were quantified using bicinchoninic acid (BCA) assay. Data-independent acquisition (DIA) proteomics identified exploratory differentially expressed proteins (DEPs), followed by functional enrichment and protein-protein interaction (PPI) network analyses. Transcript-level expression patterns and survival associations were queried in The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) datasets to provide indirect external clinical context.

Tumor regions showed higher APTw signals than peritumoral regions (p < 0.001) and increased cytoplasmic protein concentration (p < 0.05), without a corresponding increase in total or nuclear protein levels. DIA identified 654 DEPs. Further analysis highlighted 36 higher-significance DEPs, and prioritized 12 hub proteins in the PPI network. In public transcriptomic datasets, ERBB2, RUNX1, and SHC1 showed higher expression in GBM and were associated with poorer overall survival.

These findings suggest that elevated APTw signal in GBM may be associated with increased cytoplasmic protein content and distinct proteomic alterations. This imaging-proteomic framework provides exploratory regional context for future mechanistic and follow-up studies, but larger, spatially matched and independently validated cohorts are required to confirm the molecular contributors to APTw contrast.