Bioinformatics Analysis Of HOXD11 Biological Function And Significance In Glioma

Background and Objective:Gliomas originate from glial cells,including astrocytoma,glioblastoma,oligodendroglioma,ependymoma,medulloblastoma,and gliomas of other origin.Glioma has been the most common primary malignant tumor of the adult central nervous system.The World Health Organization(WHO)classifies glioma into four grades.Glioma of grade I and II is classified as Low grade glioma,while grade ? and ? is classified as High grade glioma.In clinical treatment,surgical resection plus postoperative chemotherapy and radiotherapy are the main methods,but the therapeutic effect is still unsatisfied.It has been found that the occurrence and progression of glioma are closely related to the changes of genes,which involve different processes such as gene mutation,transcriptional regulation,methylation and modification.HOX genes is the main decision development regulation,more and more studies have found that HOXD11 is closely related to the occurrence and development of a variety of malignant tumor,such as oral squamous cell carcinoma,pharyngeal squamous cell carcinoma,prostate cancer and so on.but HOXD11 role in glioma study is less,this study by tumor database comprehensive analysis,To explore the expression of HOXD11 in glioma and its influence on prognosis,to predict the signaling pathways and molecular mechanisms involved in HOXD11 in glioma,and to explore the possibility of HOXD11 as a prognostic predictor and therapeutic target of glioma.METHODS:The expression level of HOXD11 in human tumor tissues was analyzed through GEAIP website,and miRNA data of glioma in TCGA was downloaded and analyzed.The expression level of HOXD11,which is less studied at present,was analyzed and verified by using China Glioma Database(CGGA).Using R language Limma packages to analysis data,differentially expressed genes(DEGs)between normal sample and gliomas was screened,set the absolute value of ratio change |log FC|>2.0,the false discovery rate(FDR)P value is 0.05,The expression levels of HOXD11 in normal tissues and U251 and U87MG human glioma cell lines were detected by RT-PCR.Then,the expression levels of HOXD11 in different grades of glioma,IDH1 gene status and 1p/19q combined deletion state were compared in TCGA and CGGA databases,and the relationship between HOXD11 expression level and prognosis of glioma patients was explored by K-M survival analysis.Univariate and multivariate analyses were conducted with Cox regression model to further verify the prognostic value of HOXD11,and receiver operating characteristic curve(ROC)was used to test the prognostic efficacy of HOXD11.Go and KEGG were used to analyze the biological functions and pathways involved in tumor formation of HOXD11.RESULTS:Gene expression profile analysis in TCGA database showed that HOXD11 mRNA expression was up-regulated in glioma tissue compared with normal brain tissue,and the difference was statistically significant(p<0.05).Meanwhile,the result of PCR show that HOXD 11 mRNA expression in human glioma cell lines U251 and U118MG is higher than normal brain tissue's.Further analysis of TCGA and CGGA data showed that HOXD 11 mRNA expression level was correlated with WHO grade,IDH1 gene mutation status,and 1p/19q combined deletion status of glioma(P<0.001).The up-regUlated expression of HOXD11 often indicates the patients with glioma was worse comparing with the casewith low expression of HOXD11,and it is an independent factor affecting the prognosis of patients with glioma,which can predict the prognosis of patients with glioma more accurately.GO analysis showed that HOXD 11 was involved in biological processes including angiogenesis,cell division and other processes.KEGG enrichment analysis showed that HOXD 11 promoted glioma progression and affected the prognosis of patients through the P53 signaling pathway and cell cycle regulation.CONCLUSIONS:HOXD 11 is highly expressed in glioma,and the expression of HOXD 11 is significantly different in different WHO grades,IDH gene mutation status and 1p/19q chromosome deletion status,which can be used as one of the indicators for predicting glial malignancy.In terms of clinical prognosis,the high expression of HOXD 11 indicates that the overall survival of patients is short,which is an independent prognostic factor affecting glioma patients,HOXD 11 may affect tumor progression through the p53 signaling pathway,cell cycle,microvascular angiogenesis and other pathways.