Transcriptomics profiling unmasks FXYD5 and LEF1 as Central Regulators of peripheral GBM CSC relapse and immune escape
Using six primary IDH-wild glioblastomas as the source, the study examines the transcriptome differences between central core glioblastoma cancer stem cells (C-CSCs) and peripheral glioblastoma cancer stem cells (P-CSCs). Finding the molecular differences that control the behaviors, invasiveness, and possible causes of treatment resistance and recurrence in these various cell groups is the aim. The samples, which had not had any previous chemotherapy or radiation treatment, were separated into two groups: one from the central core of glioblastoma tissues and the other from the periphery. The study showed distinct transcriptome separation between P-CSCs and C-CSCs using cluster analysis, indicating distinct gene expression patterns in each sample. 52 differentially expressed genes (DEGs) were found; of these, 28 were up regulated and 24 were down regulated in P-CSCs as opposed to C-CSCs. The biological significance of these DEGs was further examined in the study, which discovered that elevated genes in P-CSCs are linked to a number of biological processes that affect the advancement of cancer, such as receptor tyrosine kinases, Wnt signaling, and ECM organization. On the other hand, P-CSCs' down regulated genes were connected to processes like cell adhesion and platelet-derived growth factor signaling. Notably, genes involved in immune evasion, drug resistance, and tumor progression, such as RIN3, FXYD5, ROBO2 and DNMT, SRC, LEF1 and RUNX3, were found to be crucial in controlling P-GSCs activity. Route analysis demonstrated the role of the ECM remodeling route, which is critical for cell motility and metastasis, and the Wnt signaling pathway in preserving stem cell characteristics. The study also found that P-CSCs expressed more genes linked to invasion, immunological regulation and extracellular matrix remodeling, all of which may encourage tumor migration into nearby healthy tissues. On the other hand, C-CSCs showed increased expression of genes linked to angiogenesis and proliferation, including EGFR and PDGFR signaling pathways, which aided in the tumor core's rapid expansion. While C-CSCs promote tumor growth through proliferative signaling, P-CSCs may be more active in invasion and immune evasion, according to the differential expression of some genes involved in these pathways. Important genes that modulate GBM behavior were identified, including those related to tumor growth (e.g., ADAMTS1, COL5A2) and the immune response (e.g., APOE). This work highlights how crucial it is to comprehend these transcriptomic variations since they could provide information on the diversity of glioma stem cells and possible targets for treatment. The results show that P-CSCs and C-CSCs play different roles in the pathophysiology of glioblastoma, and that effective therapy approaches must target both groups.