Impact of SPP1 and HMOX1 Genes in Glioma: Correlations With Oncolytic Virus Infection, Adverse Prognosis and Increased Cell Proliferation

A high death rate among glioma patients is primarily due to poor prognostic outcomes and tumour metastasis. Oncolytic viruses have gained attention as a potential therapeutic strategy as eliminating tumour cells and modifying tumour microenvironment. This research highlights the urgent necessity to investigate novel therapeutic targets and clarify molecular mechanisms in glioma. The GSE166914 dataset was analysed to examine the SPP1 and HMOX1 expression after VSV-M51 infection in glioma. By utilising the CancerSEA database, we assessed the potential function of SPP1/HMOX1 among pan-cancer. Analysis of gene/protein expression levels and clinical significance was performed to identify the roles of SPP1/HMOX1 using TCGA-glioma data. A correlation analysis was performed to screen co-expressed genes, followed by GSEA analysis. qPCR and HPA analysis were utilised to assess the mRNA/protein levels of SPP1 and HMOX1 in glioma tissues. The anti-apoptotic activity of SPP1 and HMOX1 was confirmed utilising the CCK-8 assay and flow cytometry. VSV-M51 infection resulted in SPP1/HMOX1 downregulation in T98 cells. The expression levels of SPP1/HMOX1 were significantly increased in glioma and associated with histological classifications and WHO grades. Elevated levels of SPP1/HMOX1 were related to poor prognosis in glioma. SPP1/HMOX1 was involved in influencing glioma cell motility through the PI3K/AKT, JAK–STAT and syndecan 1 signalling pathways. In vitro experiments showed higher expression levels of SPP1/HMOX1 in glioma tissues. Silencing SPP1/HMOX1 suppressed glioma cell proliferation and promoted apoptosis. In conclusion, dysregulated SPP1/HMOX1 expression was strongly related to glioma WHO grades and worse outcomes, providing deeper insights into glioma therapeutic targets and oncolytic virus-based treatments.