Screening Of Head And Neck Squamous Carcinoma Hub Genes And Associated Pathways Based On Bioinformatics Methods

Objective This study will screen the hub genes of head and neck squamous carcinoma(HNSC)and the correlation analysis of the modules,the association analysis of the hub genes and the m6 A RNA methylation modifier genes,and the analysis of the hub genes.Combined analysis of gene data validation and experimental validation,try to mine the pivot genes and related regulatory pathways related to the occurrence,development and prognosis of head and neck squamous cell carcinoma,and provide a new research angle for the diagnosis or treatment of head and neck squamous carcinoma.Methods1.Download HNSC-related datasets from the GEO database,use GEO2 R analysis,STRING platform,Cytoscape software and DIVID platform to screen out the hub genes of head and neck squamous carcinoma,construct the network interaction of gene-encoded proteins,and display the most significant associations.module.Use STRING platform and Cytoscape software to do node degree analysis of hub genes;through DAVID database,do GO functional annotation and KEGG pathway analysis of hub genes;Using the database platform Kaplan-Meier plotter to analyze the survival prognosis of the screened hub genes.2.Use TRRUST platform to analyze transcription factors in hub genes and use NCG platform to find tumor driver genes in hub genes.3.The Metascape platform tool was used to construct the interaction network between the genes associated with m6 A RNA methylation modification and the proteins encoded by the hub genes,and the GEPIA platform was used to complete the differential expression analysis and correlation analysis of the hub genes.4.Using the platform XIANTAO for data prognosis analysis and correlation analysis of head neck squamous cell carcinoma in TCGA database,experimental verification using Real-Time PCR.Results1.Screened out the MCODE module composed of 12 hub genes including DDX60,IFIT1,SERPINH1,ITGA6,COL4A2,STAT1,PLOD2,PLOD1,IFI27,COL4A5,CXCL12 and SNAI2 with significant difference in survival prognosis.2.Transcription factor SNAI2 in the module can cause tumor development and development through abnormal regulation of Hippo signaling pathway,TNF signaling pathway and PI3K-AKT signaling pathway;transcription factor STAT1 can through TNF signaling pathway,Jak-STAT signaling pathway,HIF-1 signaling pathway Abnormal regulation of Toll-like receptor signaling pathway leads to the occurrence and development of tumors.3.The tumor driver gene COL4A2 in the module affects the occurrence and development of tumors through the regulatory pathway of tumors.The specific possible path is that COL4A2 may cause the occurrence and development of tumors through abnormal regulation of the P13K-Akt signaling pathway,or through the degradation of extracellular matrix and The effect of receptor tyrosine kinase signaling to affect tumor progression;the effect of tumor driver gene IFI27 on cytokine signaling in the immune system to achieve impact on tumorigenesis and development.4.The hub genes PLOD1,PLOD2,COL4A2,COL4A5,ITGA6,SERPINH1 and m6 A methylation-related genes form an obvious regulatory association module;this regulatory module affects the head by interacting with the m6 A regulatory network Occurrence and development of cervical squamous cell carcinoma.5.The regulatory module formed by the six hub genes affects the occurrence and development of head and neck squamous cell carcinoma by affecting the expression of SERPINH1 and then the function of the m6 A regulatory network.6.SERPINH1 has a significant difference in expression,the degree of module node is high,and the correlation analysis with m6 A methylation-related genes shows that the correlation between SERPINH1 and HNRNPA2B1,METTL14,YTHDF1 is significant.SERPINH1 ROC curve AUC value of SERPINH1 is 0.959,and the performance classification evaluation effect of normal group and tumor group is extremely high.The expression of SERPINH1 has a close influence on the occurrence,development and prognosis of head and neck squamous cell carcinoma.Conclusion1.The regulatory network composed of 12 hub genes such as DDX60,IFIT1,SERPINH1,etc.,may cause the occurrence and development of head and neck squamous cell carcinoma through the abnormal regulation of related signaling pathways through the transcription factors SNAI2 and STAT1 and the tumor driver genes COL4A2 and IFI27 in the network.2.The regulatory association modules formed by PLOD1,PLOD2,COL4A2,COL4A5,ITGA6 and SERPINH1 may affect the occurrence and development of head and neck squamous cell carcinoma through the regulatory pathway of m6 A methylation modification.3.SERPINH1 is a hub gene that is resistant to the m6 A regulatory network,which can be used as biomarkers or potential treatment targets that affect the development and prognosis of head and neck squamous cell carcinoma.