| Objective: Glioma is the most common central nervous system tumor,and it is a complex process of multi-gene and environmental interaction.The current research on glioma is still relatively limited compared with other common tumors.This study screened the differentially expressed proteins in human glioma tissues of different malignant grades,combined with bioinformatics analysis to explore its relationship with glioma.Correlation and biological process,looking for key pathways in the progression of glioma,and based on previous related studies,screening out differential proteins that have further research value,and exploring them as new tumor diagnostic markers and malignant progress evaluation indicators potential.Methods: Collect pathologically confirmed low-grade(WHO Ⅰ-Ⅱ grade)glioma tissue,high-grade(WHO Ⅲ-Ⅳ grade)glioma tissue,and edema zone tissue around the tumor(non-tumor brain tissue),and divide them into The low-grade group is the 1-2 group,the high-grade group is the 3-4 group,and the non-tumor brain tissue around the tumor is the liu＿zhou group.Extract all the soluble proteins in each group of samples,use the bradford method to quantify the total protein of each group of samples,and then apply TMT(tandem mass tag quantification)technology to perform high-throughput qualitative and quantitative analysis of the proteins in the samples.The components are compared in pairs according to the ion peak intensity of the label to form 3 comparison groups,namely the first comparison group(1＿2＿liu＿zhou),the second comparison group(3＿4＿1＿2),and the third comparison group(3＿4＿liu＿zhou).<0.05 At the same time,the difference multiple is greater than 1.2 times as the screening standard.Differential protein screening,enrichment analysis(GO and KEGG),analysis of the biological processes and related signal pathways involved in the differential protein,and comprehensive analysis of the up-regulated differential proteins of the 3 comparison groups Obtain the common differentially up-regulated proteins,and analyze the interaction network between the target proteins through the STRING database,and combine the previous research results to further screen out the proteins that play a key role in the occurrence of different grades of gliomas and the progression of tumor grades.Results: A total of 31070 peptides were identified,corresponding to 5066 proteins.In the first comparison group(1＿2＿liu＿zhou),a total of 1478 differential proteins were identified,of which 933 were up-regulated and 545 were down-regulated;in the second comparison group(3＿4＿1＿2),the expression of 2168 identified proteins had significant changes Among them,1262 were up-regulated and 906 were down-regulated;in the third comparison group(3＿4＿liu＿zhou),a total of 2,317 proteins were identified,of which1328 were up-regulated and 989 were down-regulated.Through GO enrichment analysis,it is found that the differential protein in the first comparative group is mainly involved in the metabolic process related to m RNA in the biological process(BP),the metabolic process related to the endoplasmic reticulum of the biofilm,the metabolism of nitrogen compounds,organic ring compounds,and RNA processing.And decomposition,organic acid decomposition;CC(cell component)is mainly concentrated in ribosomes,mitochondrial matrix,chromosomes;MF annotation(molecular function)mainly includes ribosomal structural components,nucleic acid(DNA and RNA)combination,Nucleosome binding,transporter activity,coenzyme binding.Among the differential proteins in the second comparison group,BP is mainly involved in the regulation of blood coagulation,humoral immunity,inflammation,complement activation,extracellular matrix and structural organization,protein activation cascade;CC is mainly distributed in ribosomes,extracellular matrix,and exocrine Body,vesicle,endoplasmic reticulum,blood;MF is mainly integrin binding,extracellular matrix binding,signal receptor binding,strength extracellular matrix,peptidase activity,ribosomal structural components,enzyme inhibitor activity,and serinase activity.In the third comparative group,the BP involved in the differential protein is mainly the immune process,ion homeostasis,response to stimuli,organ development,biological regulation,anatomical structure and morphological progress;CC is mainly membrane protein complex,biological Membrane,extracellular matrix,respiratory chain,part of mitochondrial respiratory chain,secretory vesicles,oxidoreductase complex;MF is mainly transmembrane transporter activity(cation and anion transmembrane transport),serine endopeptidase inhibitor activity,ATPase transporter activity,calcium ion binding process,endopeptidase,peptidase modulator and inhibitor activity,extracellular matrix structure composition.KEGG enrichment analysis shows that the main pathways of the first comparison group are ribosomes,degradation of valine,leucine and isoleucine,systemic lupus erythematosus,synaptic vesicle circulation,bile secretion,carbon metabolism,endocrine and Other factors regulate calcium reabsorption,spliceosome,butyrate metabolism,and collecting duct acid secretion.The main pathways of the second comparison group are complement and coagulation cascade,systemic lupus erythematosus,Staphylococcus aureus infection,necrosis,carbon metabolism,ribosomes,small cell lung cancer,extracellular matrix receptor interaction,protein digestion and absorption,nerves Active ligand-receptor interaction.The main pathways in the third comparison group are Huntington’s disease,Parkinson’s disease,oxidative phosphorylation,Alzheimer’s disease,heat generation,endocrine and other factor-regulated calcium reabsorption,and non-alcoholic fatty liver disease(NAFLD),Complement and coagulation cascade,contraction of the heart muscle,retrograde endocannabinoid signal.In order to obtain more targeted proteins of interest for further discussion,Venn analysis was performed on the up-regulated differential proteins in the three comparison groups,and 86 common up-regulated differential proteins were obtained.After protein-protein interaction network analysis(PPI),it was found that most of the differentially up-regulated proteins have a tighter effect.Select the protein at the key position in the network,combined with previous literature review,there are 3proteins that are not in the field of glioma It is clearly reported that they are Copine-3protein,OAS2 protein,and Lamin B1 protein.Conclusion: Through proteomics research and review of previous studies,most of the common differentially up-regulated proteins we identified have been verified in previously reported studies.And through protein interaction network analysis,it was found that three of the proteins in key positions have not yet appeared in the field of glioma.There are clear reports,namely Copine-3 protein,OAS2 protein,and Lamin B1 protein.These proteins are up-regulated.Expression not only plays a significant role in the occurrence of gliomas of different malignant phenotypes,but also plays an important role in the progression of glioma malignancy,so it has more important research significance.Not only has the potential as a new molecular marker,but also has the potential as a treatment monitoring and evaluation indicator.This study provides a possible preliminary basis for further exploring these proteins as indicators for diagnosis and treatment of glioma and for evaluation of malignancy.Integrating the KEGG pathway analysis of the second comparison group and the third comparison group,it is found that the complement and coagulation cascade pathway may be an important pathway leading to the progression of glioma from low-grade to high-grade,and it is also persistent in high-grade gliomas.A pathway that plays an important role. |
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