Integrative Transcriptomic Analysis Identifies Hypoxia-responsive Cell Cycle Hub Genes as Prognostic Markers in Glioblastoma

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Background Glioblastoma (GBM) is the most aggressive primary brain malignancy, characterised by hypoxia-driven proliferation, therapeutic resistance and poor prognosis. While hypoxia-induced transcriptional changes are well documented, the temporal regulation of cell cycle genes under sustained hypoxia remains unclear. Purpose This study aimed to profile transcriptomic alterations induced by graded hypoxia and identify key hypoxia-responsive regulatory genes in GBM. Methods U87MG cells were cultured under normoxia and graded hypoxia (1–3 days), and experimental data of U87MG and LN229 GBM cells were utilised for validation and addressing heterogeneity. Differentially expressed genes (DEGs) were identified and analysed using STRING, Cytoscape, MCODE and CytoHubba to construct protein–protein interaction networks and extract hub genes. Functional enrichment was assessed through DAVID, ClueGO and KEGG, while prognostic relevance was evaluated using GlioVis and ONCOMINE data sets. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) validated hub gene expression dynamics. Results A total of 275 DEGs formed two main functional modules enriched in cell cycle regulation and chemokine signalling. Eighteen hub genes ( KIF20A , KIFC1 , CCNB1 , AURKA , EGR1 , CDCA3 , CENPF , CDCA2 , ASPM , KIF11 , CCL2 , CXCL8 , CCNA2 , DLGAP5 , RACGAP1 , TPX2 , PTGS2 and CTGF ) were significantly associated with mitotic processes and GBM progression. Survival analysis demonstrated that 17 hub genes correlated with poor overall survival ( p < .05). qRT-PCR confirmed that hub gene expression peaked during early hypoxia and declined with prolonged exposure, indicating dynamic regulatory adaptation. Conclusion These findings identify key hypoxia-responsive genes governing cell cycle progression and immunomodulation in GBM, highlighting their prognostic value and therapeutic potential in GBM.

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