A transcriptional network underlying migratory cellular states and reduced 5-ALA-based photodynamic detectability in glioblastoma.

Surgical resection remains the cornerstone of the standard therapy for glioblastoma (GBM), yet postoperative recurrence remains a major clinical challenge. Intraoperative photodynamic detection (PDD) using 5-aminolevulinic acid (5-ALA) improves the precision of tumor removal. However, a subset of tumor cells can evade fluorescence-based detection, potentially contributing to residual disease and relapse. The present study analyzed the relationship between cellular migratory capacity and 5-ALA PDD visibility using six patient-derived GBM cell lines (KBT#12137, KBT#10135, KBT#10170, PDM19, PDM22 and PDM123). This study revealed a positive correlation, indicating that cells with higher migratory potential accumulated lower levels of 5-ALA-induced protoporphyrin IX and were therefore more likely to escape intraoperative detection. Transcriptomic profiling identified gene expression signatures specifically associated with this phenotype, highlighting pathways related to cytoskeletal regulation, heme metabolism, and transporter activity. These findings suggest that the migratory potential and diagnostic evasion are functionally linked through shared molecular programs, thereby providing a potential basis for identifying predictive biomarkers associated with incomplete resection and recurrence risk. Overall, this study provides insights that may contribute to improved intraoperative strategies and targeted therapeutic approaches for GBM.