Construction Of A Network For Differentially Expressed Molecules In Adults And Children Of High-grade Gliomas

Background and purposeGlioma is one of the solid tumors with the highest incidence.Among them,High-Grade glioma(HGG)is considered to be the most aggressive and migratory category.It is between adults and children.A large heterogeneous tumor that occurs frequently.The heterogeneity of HGG is reflected in many aspects.For example,at the site of disease,the site of childhood tumors involves the entire brain,mainly in the middle and back of the brain,while more than 75% of adults are located in the supratentorial chamber.In terms of molecular expression,currently popular genes,such as IDH1 and MGMT,show significant mutations in adult HGG,but not in children.On the contrary,H3 is one of the histones,and its mutations often occur in children’s HGG,but rarely occur in adults.However,studies have also reported that the expression of genes such as EZH2 and WEE1 in HGG patients is significantly higher than that of normal adults and children.In terms of treatment,surgery plus radiotherapy is the current standard treatment for HGG patients.In terms of diagnosis,there is no obvious difference between adults and children.The traditional detection methods mainly depend on imaging techniques,including magnetic resonance imaging,radioisotope scanning(Y-ray brain Picture),ultrasound,computerized tomography,cerebrospinal fluid examination and postoperative pathological analysis of craniotomy.This shows that adults and children have great heterogeneity in the occurrence and development of cancer,but there is no effective means of screening in diagnosis and treatment.Due to the special location of the disease,there is currently no clear index to classify and diagnose the two before surgery.Therefore,the molecular mutation information that is differentially expressed in children and adults will be used in the diagnosis of HGG,small molecule drugs,and precision medicine.Provide meaningful theoretical support.Although there have been a large number of reports on the molecular differences between adult glioma and childhood glioma,the similarities of the molecular differences in HGG between the two populations and the significance of the differences between them between adults and children,Including message RNA(message RNA,m RNA),micro RNA(Micro RNA,mi RNA)and long non-coding RNA(Long non-coding RNA,lnc RNA)differences,there is no systematic summary and analysis.Based on this clinical phenomenon and research background,we started from the perspective of bioinformatics,collected a large number of samples in the database,analyzed the similarities and differences in molecular expression between the two populations,and paid attention to the similarities between adults and children in molecular differential expression The background of the elements and the possible diagnostic roles of molecules with common differences in HGG,including the biological processes and signaling pathways involved in similar and different molecules are summarized in detail.MethodIn this project,we first searched the detailed information of the samples in the Gene Expression Omnibus(GEO)to obtain the sequencing data of 455 samples and analyzed and integrated them.The data were analyzed and integrated.Entu takes the intersection method and lists in detail the m RNA,mi RNA,and lnc RNA molecules that are common and different between children and adults.Then divide the data into three groups,namely: the common difference molecular group between children and adults,the independent difference molecular group for children,and the independent difference molecular group for adults.Then use these difference data to calculate the biological pathways involved in each group in the Cotyscape software,and then use the three sets of data on the protein interaction(Protein Protein Interaction,PPI)online website to calculate the protein connections corresponding to each m RNA element.Create a protein network interaction map.And to point to the m RNA contained in the pathway as the core m RNA.Finally,use The Cancer Genome Atlas(TCGA)database to download and analyze the original tumor data of 577 cases,collect m RNA and mi RNA expression data and follow-up information of large quantities of glioma samples,and combine R language and Perl script to pair After the data is matched,the survival curve of the core molecule is verified,and the mi RNA and m RNA with statistical significance are found.Finally,with mi RNA as the core,draw the lnc RNA-mi RNA-m RNA network diagram under the condition of the common differences between adults and children with HGG as the disease background.ResultsWe found that there are 7 mi RNAs and 35 m RNAs with common differences between adults and children,35 mi RNAs and 111 m RNAs with independent differences in adults,and 42 mi RNAs and 116 m RNAs with independent differences in children.These data are drawn into three groups of networks according to the upper and lower adjustments.We draw a heat map of the differential mi RNA based on the amount of expression.These results more systematically expand the researchers’ understanding of molecular mutations in HGG in children and adults.Through the enrichment calculation of pathways in Kyoto Encyclopedia of Genes and Genomes(KEGG),we conclude that the genes that are commonly up-regulated are mainly involved in the micro RNA pathway in cancer;the genes that are jointly down-regulated are mainly involved in neuroactive ligands-Receptor interaction,cocaine addiction and nicotine addiction,etc.The genes that are independently differentially up-regulated in adults are mainly enriched in ECM receptor interactions,focal adhesions,protein digestion and absorption,proteoglycans in cancer,platelet activation and PI3K-Akt signaling pathways;independent down-regulation of major enrichment and co-down-regulation of genes Related to synapses,synaptic parts and cell connections.Children’s independently up-regulated genes are concentrated in the synaptic vesicle cycle pathway,while children’s independently down-regulated genes are mainly involved in Hippo signaling.The interpretation of the biological pathways of each group in the tumor enriches our significance for the molecular expression of HGG in children and adults.ConclusionWe screened a total of 3 mi RNAs: mi R-10 a,mi R-10 b,mi R-139 and CDK6,SOX4,VEGFA,etc.including 6 m RNAs and 12 lnc RNAs.And the core molecule and related target molecules constitute the network diagram of lnc RNA-mi RNA-m RNA.The verification of the survival curve of the core molecules greatly suggests the basis for their biomarkers and therapeutic targets in adult and children HGG.