| BackgroundGlioma is the most common primary central nervous system tumor in adults.According to the standard of histology,gliomas are divided into four grades(???)with increasing malignancy by WHO.In recent years,the comprehensive diagnosis and treatment mode of glioma surgery combined with chemoradiotherapy has made great progress.However,because of its high incidence rate,strong invasion,long course,rapid progress,easy relapse,poor prognosis,etc.,accurate diagnosis and precise treatment of glioma are still the most important and urgent research topics in the department of neurosurgery.It is worth noting that the detection rate of glioma in the elderly is increasing year by year,and the particularity of the elderly patients in group characteristics,individual differences,treatment tolerance and other aspects makes the clinical diagnosis and treatment of the elderly glioma population more challenging.How to help the elderly patients with glioma to receive more comprehensive and reasonable treatment and achieve better treatment effect is an important direction in the research process of glioma.In addition,clinicopathological factors,imaging features,genomics and immunological mechanisms are of great value in guiding and predicting the overall diagnosis,treatment and prognosis of gliomas.Elderly patients with gliomas have representative potential characteristics and clinical significance in these aspects,but few systematic studies on these characteristics,significance and basic mechanisms.Therefore,it is of great clinical and social significance for the early diagnosis,precise treatment and comprehensive management of the elderly glioma population to explore the characteristics and laws of the elderly glioma in clinical pathology,imaging,genomics and immunology,and to analyze and explain the prognosis of the elderly glioma patients.ObjectivesThe purpose of this study is to reveal the course characteristics and prognostic significance of glioma in the elderly from the perspectives of clinical pathology,imaging,genomics and immunology,to find out the possible targets of the onset and progress of glioma in the elderly,and to explore and demonstrate its potential mechanism.Methods596 patients with WHO grade ? to ? diffuse glioma were included in this study.There were 464 cases in the elderly group(over 60 years old)and 132 cases in the young group(under 60 years old).The clinical and imaging data of the patients were collected and the molecular pathology(IDH mutation,TERT promoter mutation and 1p/19q codeletion)was detected.Chi square test was used to compare the differences among the groups.Univariate and multivariate analysis were used to evaluate the prognosis of different groups and to find independent predictors.In addition,a series of age-related genes were identified and screened in glioblastoma(GBM)to construct GBM subtypes with different prognosis.The differences of GBM subtypes in tumor microenvironment(TME)cell infiltration,immune related gene expression and CNV were compared.Finally,189 glioma patients of different age groups were screened and enriched by R language and Metascape website to explore the gene expression characteristics and potential related signal pathways.ResultsBy comparison,we found that there were significant differences in WHO grade(P<0.001),histological type(P<0.001),Ki67 index(P<0.001),molecular subtype(P<0.001),IDH mutation(P<0.001),TERT promoter mutation(P=0.006)and 1p/19q codeletion(P<0.001)between the elderly group and the young group.In addition,the results also showed that the poor prognosis of elderly low-grade gliomas(LGGs)was due to the deep location of the tumor,the obvious enhancement of the solid part of the tumor and the serious peritumoral edema.Through the identification and screening of a series of age-related genes,they were divided into two optimal clusters,named C1 and C2 respectively.The prognosis of the two groups was significantly different(P<1e-5).Three common genes RABP17,IGFBP5 and HDHD3(Padj<0.001)were screened from TCGA and GPL96 databases,which were all related to the prognosis of GBM patients(P<0.05).There were significant differences in TME score,immune activating gene,immune checkpoint gene and TGF/EMT pathway related gene expression between C1 group and C2 group(P<0.05).The CNV of SEC61G(P=0.00017)and SLC25A20(P=0.02709)was significantly correlated with the prognosis of gliomas.In addition,217 differentially expressed genes were screened from 57774 sequenced genes(P<0.05 and multiple?1.5),including 198 up-regulated genes and 19 down-regulated genes.The differentially expressed genes were enriched in the"receptor regulatory activity" pathway of GO,the "IL-17 signaling pathway" of KEGG,the "chemokine receptor binding chemokine" and the "common pathway of fibrin clot formation" of Reactome.ConclusionsThe clinical,pathological and imaging features of gliomas in the elderly are different from those of patients under 60 years old.The relatively deep location of the tumor,the obvious enhancement of the solid part of the tumor,and the serious edema around the tumor are the imaging features that predict the poor prognosis of low-grade gliomas in the elderly.GBM data from public databases were used to identify and cluster age-related genes.There were significant differences in TME scores and expression of immune related genes between different groups,and they were related to prognosis.CNV is also one of the factors that affect the prognosis of GBM patients.To some extent,these data explain the influence of age on the prognosis of GBM patients,and provide a new strategy for immunotherapy and gene therapy of GBM.In addition,the gene expression of gliomas in the elderly has its own specificity.The differentially expressed genes screened have related enrichment pathways in GO,KEGG and Reactome. |
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