Identification Of Signatures In High Grade Gliomas Based On Gene Expression Profiles

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Lnc RNA profile study reveals four-lnc RNA signature associated with the prognosis of patients with anaplastic gliomasBackground and objective Anaplastic glioma(AG)is Grade ?,the median overall survival(OS)was approximately 37.6 months.Due to the varied OS in AG patients,there are other factors that affect the prognosis of these patients.Methods We included three glioma datasets(GSE16011,CGGA and REMBRANDT)and extracted the long non-coding RNA(lnc RNAs)expression profiles.We further screened the prognostic lnc RNAs based on the expression of lnc RNAs and the clinical information of AG patients using bioinformatics analyses.Results Based on the lnc RNAs expression profiles,we screened four lnc RNAs(AGAP2-AS1,LINC01198,TPT1-AS1 and MIR155HG).According to the four lnc RNAs expression,we constructed the risk score and AGs can be divided into two groups(low risk group and high risk group)using the median risk score.The OS in the low risk group was significantly longer(median OS 2208.25 days vs.591.30 days,P < 0.0001)and it was similar to the OS in Grade ? gliomas(P = 0.1669),while the OS in high risk group was significantly different to that in Grade ? gliomas(P = 0.0005).Therefore,AGs can be divided into Grade ? like and Grade ? like groups based on the four lnc RNAs signature.The signature could be an independent prognostic factor using the multivariate analysis(P = 0.000).The expression of AGAP2-AS1,LINC01198 and MIR155 HG increased with glioma grade,while TPT1-AS1 was decreased.Knockdown AGAP2-AS1 could significantly inhibit cell proliferation,migration and invasion,and increase the apoptosis in vitro.Conclusions The four lnc RNAs signature has prognostic value for AG patients.Therefore,the individual therapys should be taken to achieve the best treatment and reduce the side effects for AGs.Part ? An Immune-Related Lnc RNA Signature for Patients with Anaplastic GliomasBackground and objective There is a distinct immune status in different grades of glioma and the differentially expressed long non-coding RNAs(lnc RNAs)have prognositc values for gliomas.Therefore,immune related lnc RNAs can be used as therapeutic targets for anaplastic glioma(AG)patients.Methods We extracted the lnc RNAs expression profiles from three glioma datasets(CGGA,GSE16011 and REMBRANDT).The co-expression network of immune related lnc RNAs was constructed based on the expression of lnc RNAs and immune genes.We further screened the prognostic immune related lnc RNAs.Gene set enrichment analysis(GSEA)and principal component analysis(PCA)were used to explore functional annotations of the identified lnc RNAs.Results A total of 572 lnc RNAs and 317 immune genes were screened and constructed the co-expression network to identify immune related lnc RNAs.We identified 9 immune related lnc RNAs(SNHG8,PGM5-AS1,ST20-AS1,LINC00937,AGAP2-AS1,MIR155 HG,TUG1,MAPKAPK5-AS1 and HCG18)in AG patients.The findings were validated in two independent databases(GSE16011 and REMBRANDT).AGs can be divided into two groups(low risk group and high risk group)based on the expression of these 9 lnc RNAs.The overall survival(OS)and the progression free survival(PFS)in the low risk group were significantly longer than those in the high risk group(P <0.0001;P <0.0001).The high risk group displayed no-deletion of chromosomal arms 1p and/or 19 q,isocitrate dehydrogenase wild-type,classical and mesenchymal TCGA subtype,G3 CGGA subtype,and lower Kanofsky performance score(KPS).The signature could be an independent prognostic factor for AGs(P = 0.000,risk ratio(HR)= 1.434).The results were further conformed in two independent databases(GSE16011,REMBRANDT).Based on PCA analysis,AGs in two groups showed different immune states.Conclusions We screened 9 immune related lnc RNAs and the signature could be a biomarker for AG patients.Part ? A three-gene signature for prognosis in patients with MGMT promoter-methylated glioblastomaBackground and objective Glioblastoma(GBM)is a malignant tumor of the central nervous system with high mortality rate.The methylation status of O(6)-methylguanine DNA methyltransferase(MGMT)promoter can determine the chemo-sensitivity of GBMs.However,there are still other factors affecting the prognosis of MGMT methylated GBMsMethods Our study included three glioma databases,m RNA microarray,RNA seqencing data from Chinese Glioma Genome Atlas(CGGA)and RNA seqencing data from The Cancer Genome Atlas(TCGA).Bioinformatics analysis was carried out using DAVID software(The Database for Annotation,Visualization and Integrated Discovery).Results Three prognostic genes were identified based on three datasets and the risk score was further constructed.GBM patients with MGMT methylated can be divided into two groups(low risk group and high risk group)using the median risk score.It showed that GBMs in the low risk group had significantly longer overall survival(OS)than those in the high risk group(median OS 1074 vs.372 days,P = 0.0033).The signature can significantly distinguish GBMs stratified by MGMT methylation and chemotherapy(P = 0.0473),while there is no significant difference for GBMs in low risk and high risk group or unmethylated MGMT GBMs without chemotherapy.The signature was an independent prognostic factor(P = 0.004)using multivariate COX analysis.Conclusions This study indicated that the signature,was identified based on bioinformatics analyses,has significant prognostic value for MGMT promoter methylated GBM patients.Part ? Long Non-coding RNA LINC00152 is a Potential Prognostic Biomarker in Patients with High-grade GliomaBackground and objective Dysregulated long non-coding RNAs(lnc RNAs)are associated with the progression of gliomas.High-grade gliomas(HGGs)include Grade ? and Grade ? gliomas.The median overall survival(OS)of Grade ? gliomas is 37.6 months,while Grade ? gliomas is approximately 14 months.The role of LINC00152 in HGGs remains unclear.Methods Our research included three glioma databases,Chinese Glioma Genome Atlas(CGGA)microarray,CGGA RNA sequencing and GSE16011.We evaluated the expression and prognostic value of LINC00152 in HGGs with clinical information.The functions of LINC00152 in the development and progression of glioma were disclosed in vitro and in vivo.Results The expression of LINC00152 was increased with glioma grade and was the highest in the TCGA mesenchymal subtype.LINC00152 can independently predict the prognosis of HGGs in the CGGA microarray database.The overall survival(OS)in the LINC00152 high expression group is significantly shorter than that in the low expression group(median OS 14.77 months vs.9.65,P = 0.0216).The above results can be further verified in two independent databases.The clinical and molecular features of HGGs showed that LINC00152 high expression patients displayed TCGA mesenchymal type,older(? 46 years),isocitrate dehydrogenase1 wild-type(IDH1-WT),O(6)-methylguanine DNA methyltransferase(MGMT)unmethylated,non-chemotherapy and low karnofsky performance status(KPS).Based on the expression of LINC00152,we screened 4288 probes(2519 up-regulated;1769 down-regulated).The results showed that the up-regulated genes were enriched in the immune response,apoptosis process,cell adhesion and regulation of cell proliferation using DAVID software(The Database for Annotation,Visualization and Integrated Discovery).Knockdown LINC00152 can significantly inhibit cell proliferation,migration and invasion,and enhance the sensitivity to chemotherapy in vitro.Knockdown LINC00152 could significantly inhibit the growth of tumor in vivo.Conclusions LINC00152 could be a potential biomarker for the prognosis of HGG patients.