Bioinformatic Screening Of Differentially Expressed Genes And Related Mechanisms In Gliomas

Glioma is a higher incidence of cancer which could be divided into severalsubtypes. Gene expression and mutations of various types of glioma are not thesame. So research to clarify the pathogenesis of a variety of gliomas and thedifferent grades of the same subtype of glioma is of great significance. In this study,several bioinformatics analysis of three different grades of glioma were performed,including DEGs screening of different degree of glioma, protein-protein interactionnetwork analysis and pathway enrichment analysis. This study was attempted tofurther clarify the pathogenesis of different grades of tumor glioma.Microarray expression data GSE4290(23samples from epilepsy patients areused as non-tumor samples.157tumor samples include26astrocytomas,50oligodendrogliomas and81glioblastomas) and GSE15824(30brain tumorsamples including15glioblastomas,8astrocytomas and7oligodendrogliomas,10glioblastoma cell lines and5normal brain samples) were obtained from the GEOdatabase both with the platform of GPL570. Total81glioblastoma samples ofGSE4290were belong to grade IV glioma,7of26astrocytoma samples were gradeII and other19were grade III. Total50astrocytoma samples included38grade II and12grade III samples.Data preprocessing and differentially expressed genes (DEGs) analysis withrobust multi-array analysis (RMA) analysis and significance analysis of microarrays(SAM) analysis (GSE4290) or limma package (GSE15824) were performed,respectively. In the SAM analysis, total23non-tumor samples as the controlsamples and the experimental groups including3subgroups of grade II, III and IV;while GSE15824were divided into three experiment groups including astrocytoma,glioblastomas, oligodendrogliomas and the control group.It was found that there were similar fold changes of gene expression amongthree subtypes of glioma. Besides, multiple common DEGs including up-anddown-regulated genes were shown in different three subtypes of glioma. Moreover, the higher thegrade of glioma, the greater the number ofDEGs and the highermultiples of differential genes expression.In addition, multiple common GO terms (e.g. response to wounding) wereenriched by DEGs in different subtypes of glioma. Furthermore, co-expression geneand co-regulated gene screening analysis identified some common genes (e.g. SRF).These results revealed thatdifferent subtype gliomacould have multiplecommonmolecular mechanism. Therefore, systematically analysis of differentsubtype glioma into different grades could be practicable. Similar up-regulatedDEGs of three different grade of tumors as: epidermal growth factor receptor (EGFR)and the sex-determining region Y box protein11(SOX11), etc., and thedown-regulated DEGs as: γ-aminobutyric acid A receptor5(GABRA5) andsomatostatin (SST), etc. These results suggested that different grades of giliomapossessed common DEGs, and may also involved in the DEGs related molecularmechanisms.The Short Time-series Expression Miner (STEM) was used to classify DEGs.Nine important gene classification were obtained, among which, genes of cluster1,6,7,8and9appeared earlier (grade=2), followed by cluster3and4(grade=3),and cluster2and5were the last (grade=4). These results suggest that genes ofthese three grades involved in different process of glioma progression.The STRING and KEGG enrichment were combined with EnrichNet for PPIand pathway analysis. The results shown some higher degree of nodes, such astumor protein p53(degree=129), CD44molecule (degree=105), EGFR (degree=100), and so on. Subsequently, six significantly enriched pathways (q-value <0.05)were obtained with the KEGG pathway analysis. The first two pathwaysrespectively were ECM-receptor interaction and Long-term potentiation. Hub nodes(e.g. SV2, Collagen and HLA) of ECM-receptor interaction pathway were mainlyrelated with cell migration, invasion and immune response. Important genes ofLong-term potentiationwereN-methyl-D-aspartate receptor (NMDA receptors)andmetabotropicglutamatereceptor (mGluR5), etc. There was only one up-regulatedsites of NRAS with a small FC of1.015. These DEGs and gene-related pathwaysmay play important roles in the occurrence and development of glioma.In conclusion, this study illustratedthat many similar or identicalmolecularmechanisms between different subtypes of gliomas were existed. There were similarities inimportant genes and molecular mechanismsof different gradegliomas.ECM-receptor interaction and Long-term potentiation and their respectiverelated genes may have important biological significance in the development ofglioma.These current studycouldbe very important for the understanding ofthetumorigenesis and is valuable for further preventionand treatment of glioma.