Identification Of Glioma Biomarkers

Purpose: In the present study,we aimed to identify potential biomarkers to provide new strategies for the treatment and diagnosis of glioma patients.Materials and Methods: Based on GSE16011 and GSE4290 in the GEO database and analysis of differential genes through the R “limma” package,GO and KEGG enrichment analyses were performed using the "cluster Profiler" R package.The PPI network was constructed with the STRING tool and visualized using Cytoscape.The MCODE plugin was used to analyze the subnetwork,cyto Hubba was used to calculate the Node score.The survival and relationship of the hub genes with malignant and IDH mutations were verified in TCGA and CGGA.The glioma cell lines U308 and U87 MG were used for in vitro studies.Gene expression was downregulated with si RNA,which was verified by RT-qPCR.EdU and CCK8 assays were used to detect cell proliferation.Transwell assays were used to study migration and invasion.Western blot analysis detected proteins in related pathways and downregulated target genes.Result: We obtained the following 8 hub genes through bioinformatics analysis: LOX,POSTN,FN1,VEGFA,CD44,SERPINE1,SERPINH1,and FSTL1 and verified that increased expression of the hub genes was associated with poor prognosis and high malignancy in glioma patients in TCGA and CGGA.The expression of hub genes in IDH-mutant glioma patients was lower than that in IDH wild-type glioma patients.We performed in vitro experiments on FN1,SERPINH1,and FSTL1 and confirmed that FN1,SERPINH1 and FSTL1 promoted cell proliferation,migration and invasion in U308 and U87 MG glioma cells.We examined NF-k B and PI3K-Akt signaling pathway-related molecules and found that p-Akt and p-P65 decreased after inhibition of FN1 expression.After SERPINH1 was silenced,the expression of P65 and p-P65 decreased.The expression of P65 and p-P65 decreased after downregulation of FSTL1.Conclusion: In the present study,we conclude that FN1,SERPINH1,and FSTL1 regulate proliferation,migration and invasion through the NF-k B and PI3K-Akt signaling pathways and can be used as biomarkers for the treatment and prognosis of glioma patients.