Public Database Based On Screening Of Prognosis-related Genes In High-grade Gliomas And Analysis Of Their Clinical Prognostic Factors

Background Glioma is the most prevalent primary malignancy of the central nervous system,and high-grade gliomas have a poor prognosis due to their high pathological grade,infiltrative growth and poor treatment response.Although new treatment modalities such as immunotherapy,targeted therapy and electric field therapy have been proposed based on the application of the standard Stupp protocol,the median survival of glioblastoma,the most common form of high-grade glioma,is only 8 months.The application of immunotherapy and targeted therapy modalities,which have continued to break through in other solid tumor studies,is facing difficulties in high-grade glioma.Therefore,the search for molecular phenotypes characteristic of high-grade gliomas may become an important approach to unlock the dilemma of glioma treatment.Integrin-binding protein(IBSP)is involved in bone metastasis in breast,lung and prostate cancers.However,the role of IBSP in glioma has not been previously reported.Therefore,our study focused on investigating the role and mechanism of IBSP as a biomarker in the malignant progression of glioma.Objective To analyze and compare the relationship between IBSP expression and clinical features in patients with high-grade glioma,as well as the relationship between IBSP expression and pathological grading of high-grade glioma,and to explore whether the prognosis of high-grade glioma can be judged by differences in the expression of IBSP.To explore the possible mechanisms of IBSP involvement in the pathogenesis of high-grade glioma by searching for genes associated with IBSP and enrichment in related signaling pathways.As well as to analyze the clinical factors affecting prognosis of high-grade glioma,which in turn will provide assistance in the prevention,treatment and judgment of prognosis of high-grade glioma,with the ultimate hope of achieving survival rate and quality of life in high-grade glioma.Results IBSP expression was elevated in gliomas and increased with WHO pathological grading.In addition,IBSP expression was increased in IDH-wild-type type,1p19 q non-co-deficient state.In a multifactorial regression analysis,IBSP was an independent factor affecting the prognosis of gliomas in different databases(HR=1.531;CI1.07-2.192;P=0.020);the results of gene enrichment analysis showed that IBSP was involved in processes such as apoptosis,coagulation and complement pathways.CASP4,KYNU,MSR1,PLAUR,SIGLEC9 and SLC16A3 are genes that are positively associated with IBSP expression and were found to be involved in the pathogenesis of glioma.The results of immunohistochemical staining showed increased expression of IBSP in high-grade gliomas relative to low-grade gliomas(P < 0.001).In univariate and multifactorial analyses of clinical factors associated with prognosis in patients with high-grade gliomas,methylation of the MGMT promoter region(HR = 0.239;95% CI:0.098 to 0.583;P < 0.001),preoperative concomitant epilepsy(HR = 0.193;95% CI:0.076 to 0.488;P < 0.001)and the number of postoperative chemotherapy sessions(HR= 0.845;95% CI: 0.773 to 0.924;P < 0.001)were independent protective factors for OS.Conclusions IBSP expression is an independent prognostic factor contributing to poor prognosis in gliomas.This study revealed potential molecular mechanisms of IBSP in glioma pathogenesis,and IBSP could be a potential therapeutic target to improve glioma prognosis.Clinical prognostic analysis found a protective effect of pre-surgical seizure symptoms in patients with high-grade gliomas,and methylation of the MGMT promoter region and chemotherapy help improve the prognosis of high-grade glioma patients,but still need to be validated in multicenter clinical studies.