Bioinformatics Analysis Of Gene Expression And Signal Transduction Pathway In NK/T Cell Lymphoma,Nasal Type

Objective: NK/T cell lymphoma(NKTCL),nasal type,is a group of rare malignant lymphomas derived from NK cells or T cells.The disease progesses rapidly and the prognosis is poor.According to recent studies,the median survival time of nasal NKTCL,is only 37 months.Treatment options include chemotherapy,radiation therapy,and hematopoietic stem cell transplantation.The incidence of nasal NKTCL is associated with Epstein-Barr virus(EBV)infection,genetic abnormalities,chromosomal abnormalities,signaling pathways and abnormal protein expression abnormalities.Gene abnormalities,including gene mutations and deletions,can affect cell proliferation,differentiation,apoptosis and signal transduction.In this study,we use the information resources provided by the database and the method of bioinformatics to study nasal NKTCL,try to find out the biological characteristics,and further understand the pathogenesis,eventually find out the biomarkers and the pathways involved in the development process.This study provides a theoretical basis for the molecular mechanism research and development of molecular targeted drugs for the occurrence and development of nasal NKTCL.Method: The gene expression data,series GSE80631 and GSE19067,was downloaded from GEO(Gene Expression Omnibus)database.The original data was analyzed by the GEO2 R tool and the up-regulation and the down-regulation of the genome group were identified as differentially expressed genes(DEGs).Then,these DEGs were analyzed by GO(Gene Ontology)analysis and KEGG(Kyoto Encyclopedia of Genes and Genomes)pathway enrichment analysis,to explore the molecular function,the biological processes involved,the location of the cells,and the signaling pathways in which they are located.The DEGs were input into the STRING database to evaluate the correlation of gene products,and analyze the interaction between proteins.The PPI(protein-protein interaction)network of DEGs was constructed by Cytoscape software to search for central genes with marker functions.MCODE plug-in was used to scan the PPI network and screen the modules with significant effects.Then the genes in the modules were enriched and analyzed again to obtain signaling pathways with significant effects.Results: 1.The analysis showed that there were 254 differentially expressed genes in nasal NKTCL samples compared with normal samples,including 212 up-regulated genes and 42 down-regulated genes.2.GO functional annotations show that:(1)The biological processes(BP)of up-regulated genes mainly enrich in regulation of cell motion,inflammatory response,response to wounding,etc.;the biological processes of down-regulated genes mainly enrich in cellular response to stress,DNA replication,DNA repair,etc.(2)The cell components(CC)of up-regulated genes mainly enrich in plasma membrane,extracellular region part,receptor complexe,etc.;the cell components of down-regulated genes mainly enrich in intracellular organelle lumen,mitochondrial lumen,mitochondrial matrix,etc.(3)The molecular function(MF)of up-regulated genes mainly enrich in chemokine activity,growth factor binding,cytokine binding,etc.;the molecular function of down-regulated genes mainly enrich in structure-specific DNA binding.3.KEGG pathway analysis show that the DEGs mainly enrich in cytokine-cytokine receptor interaction,chemokine signaling pathway,pathways in cancer,hematopoietic cell lineage,endocytosis,etc.4.By constructing PPI network,the first 14 central genes were obtained as follows: SRC,EGFR,MMP9,CXCL12,CXCL10,CD34,ESR1,PCNA,CXCL9,CSF1 R,CXCL1,CXCR2,CCL21,FOXO3.These genes were mainly concentrated in chemokines and cell migration-related processes.The three most significant PPI models were screened by MCODE plug-in of Cytoscape,which were enriched in chemotaxis,cytokine activity,defense response,cell motion,and pathways associated with protein amino acid autophosphorylation,protein kinase activity,and a variety of cancer-related pathways such as bladder cancer.Conclusion: 1.Chemokines,including CXCL12,CXCL1,CXCL9,CXCL10,CXCR2,CXCL16 and CCL21,play an important role in the occurrence and development of nasal NKTCL.The up-regulation of CXCL9 and CXCL10 may be related to the predisposition of nasal NKTCL to hemophagocytic syndrome.3.Other genes such as SRC,EGFR,MMP9,CD34,PCNA,FOXO3 are central genes with marker functions.These genes may closely relate to the occurrence and development of nasal NKTCL.