Identification Of A Panel Of Genes As A Prognostic Biomarker And Drug Intervention For Glioblastoma Multiforme

Background and AimsGlioblastoma multiforme is a common fatal tumor of the central nervous system,accounting for 60?70%of gliomas,which belongs to high-grade gliomas.GBM has the characteristics of high mortality and recurrence rate.Even with active clinical treatment,the survival rate of patients is still low.The mechanism of GBM and effective treatment are currently a research hotspot.With the deepening of research,more and more biological characteristics and new therapeutic targets of GBM have been found gradually.Many studies have confirmed that multiple signaling pathways are involved in the generation,development,drug resistance and recurrence of GBM.But at present,the survival prediction and treatment for GBM patients are still not ideal.Because the molecular mechanism of GBM resistance is still unclear,sensitive and accurate GBM biomarkers can not only be used to guide targeted therapy,but also effectively predict the prognosis of patients,providing a basis for defining diagnosis and treatment targets,formulating individualized treatment programs.In addition,because GBM is insensitive to conventional treatment,the development of therapeutic drugs with clinical efficacy has become an imminent problem.Salinomycin has been found to have the effect of anti-cancer stem cells,and its therapeutic effect on breast cancer stem cells is even more than 100 times higher than that of paclitaxel,a traditional anti-cancer drug.Based on the above reasons,this paper will screen and identify the prognostic biomarkers of GBM,and verify the role of salinomycin in anti-GBM therapy through cell experiments.Methods and ResultsThis study first explored the correlation between CD44 and the prognosis of glioblastoma multiforme,and the effect of down-regulation of CD44 on the proliferation of glioblastoma multiforme cells.The relationship between CD44 and survival time of patients with glioblastoma multiforme was analyzed by using TCGA database and R2 gene analysis visualization platform.The expression of CD44 was inhibited by siRNA interference,and the effect of CD44 down-regulation on proliferation of glioblastoma multiforme cells was detected.It was found that the prognosis of patients with high expression of CD44 was worse.Downregulation of CD44 could significantly inhibit the proliferation of glioblastoma cells.Secondly,we screened the genes highly co-expressed with CD44 in GBM tissues,analyzed their relationship with the prognosis of GBM,and determined the genome of the prognostic biomarker of GBM.The results showed that ABCC3,TNFRSF1A and CD44 were highly co-expressed in GBM tissues,and the expression levels of CD44,ABCC3 and TNFRSF1A were significantly higher than those in non-tumorous brain tissues.Furthermore,the effect of salinomycin on GBM cells and stem cells was verified.The effects of salinomycin on the proliferation,migration and death of GBM cells and the proliferation of GBM stem cells were detected.The effects of salinomycin on the expression of CD44,ABCC3 and TNFRSF1A protein and gene in GBM cells were also detected.The results showed that salinomycin could effectively inhibit the proliferation,migration and promote the death of GBM cells,and inhibit the proliferation of GBM stem cells.Salinomycin could down-regulate the expression of CD44,ABCC3 and TNFRSF1A protein and gene.Finally,whether triptolide can sensitize salinomycin to kill GBM cells and stem cells was tested to reveal the significance of triptolide combined with salinomycin.The effects of salinomycin and triptolide on the proliferation of GBM cells and their stem cells were detected,and the combined effects of triptolide and salinomycin were evaluated.The results showed that triptolide combined with salinomycin could kill GBM cells and their stem cells.ConclusionsThe expression level of CD44 can be used as a sensitive predictor of the prognosis of glioblastoma multiforme and a potential therapeutic target;CD44,ABCC3 and TNFRSF1A can be combined with MGMT to form a four-gene model for predicting the response of GBM patients to traditional anti-GBM therapy;salinomycin has a strong effect on GBM cells and stem cells,and triptolide can combined with salinomycin to kill GBM cells and stem cells,which is a potential chemosensitizer.