| Thyroid cancer is one of the fastest growing and most common endocrine malignant tumors in the world.In recent decades,the world incidence of thyroid cancer has increased significantly.Thyroid cancer is also the fifth most common cancer among women,and the probability of women suffering from cancer is three times that of men.Due to the complex disease progression of thyroid cancer,predicting potential biomarkers of this cancer remains a huge challenge.Based on the multi-omics data of thyroid cancer in the TCGA database and GEO database,as well as some newly developed specific biological data repositories,the key ncRNA and potential immune-related molecular markers in thyroid cancer were mined through gene differential expression analysis,biological network construction and gene downstream analysis,and the molecular mechanism of thyroid cancer was explored in this research.The main contents include:Firstly,gene differential expression analysis identified 1092 differentially expressed lncRNA,124 differentially expressed miRNA,1750 differentially expressed mRNA(DEmRNA)and 24 differentially expressed circRNA.Then,two ceRNA networks of lncRNAmiRNA-mRNA and circRNA-miRNA-mRNA were constructed by using bioinformatics auxiliary analysis tools such as star Base,collectively referred to as NCceRNA network.Then,the hub genes were screened by calculating the topological attributes of nodes in the network,and a ceRNA sub-network consisting of hub genes with hsa-mir-221,hsa-mir-372 and hsa-mir-363 as the core was constructed.Subsequently,the prognostic value of these three miRNA was evaluated,and the target genes regulated by them were analyzed by bioaccumulation.Secondly,a protein-protein interaction(PPI)network was constructed based on the DEmRNA contained in the NCceRNA network,and the MCODE clustering function module analysis was performed on the network.There were five central nodes in the PPI network,including CCND1,CDKN1 A,CDK4,HGF,and KIT.Three important molecular complex modules with a score of score?4 in the PPI network were subsequently detected by MCODE.Module 1 is mainly related to cell cycle and cell proliferation,and the over-activation of cyclin E/CDK2 complex may be an important mechanism for tumor resistance.Module 2 was mainly related to synaptic vesicles and vesicles,as well as synaptic exocytosis and endocrine exocrine secretion,and might be closely related to tumor migration and invasion.Module 3 is mainly closely related to immune-related drivers,inflammatory cells and tumor microenvironment(TME),and may be a potential biomarker for immunotherapy of thyroid cancer.Subsequently,enrichment analysis was performed on the above three important PPI network modules,and it was found that the functions and pathways enriched by the genes contained in the modules were highly consistent with the impact of the modules on tumor progression.Thirdly,18 key genes(KGs)and 6 key pathways(KPs)were identified based on 8 FDAapproved thyroid cancer drugs,116 drug targeting genes and 153 disease genes.Then,bioenrichment analysis of 18 KGs was performed to determine dysfunction pathways mainly involved in THCA.Further,crosstalk analysis of KPs was carried out and it was found that abnormal activation of receptor tyrosine kinase can activate the entire pathway crosstalk mechanism,which is also the key site of targeted therapy.Integrin can activate focal adhesion and PI3K-Akt pathways,and affect cancer migration.Activation of the Ras,Rap1,and focal adhesion pathways will overactivate the downstream MAPK and PI3K-Akt pathways,resulting in malignant tumor progression.Genetic changes in membrane receptors in the EGFR tyrosine kinase inhibitor resistance pathway also overactivate the downstream MAPK and PI3K-Akt pathways,thereby promoting cancer cell proliferation and differentiation.Fourthly,single-sample gene-set enrichment analysis(ss GSEA)was used to score the cancer samples in the transcriptome data downloaded from the TCGA database and the patients were divided into high,medium and low immune groups by immune classification combined with hierarchical clustering.The ESTIMATE algorithm and the CIBERSORT deconvolution algorithm were used to analyze the tumor microenvironment and the degree of immune cell infiltration of the thyroid cancer samples.Through difference analysis,62 immune-related differential genes(IDEGs)were screened out,and 9 immune-related transcription factors(IDTFs)were screened out through transcription factor(TF)enrichment analysis and difference analysis,which could be used as immunotherapy markers of thyroid cancer,including RUNX3,AR,PROX1,IRF8,PBX4,TP63,RUNX1,FOXA2 and RARB.In addition,the biological pathway closely related to IDTFs is the interaction between cytokines and cytokine receptors,and the immune cells are dendritic cells,which are closely related to the immune response of thyroid cancer,thus providing the basis for further exploration of immunotherapy for thyroid cancer.In conclusion,based on the multi-omics data of thyroid cancer in the TCGA database and GEO database as well as some newly developed specific biological data repositories,the dataset of this study was constructed through data pretreatment.Through the construction and analysis of ceRNA network,it was found that the ceRNA sub-network with hsa-mir-221,hsa-mir-372 and hsa-mir-363 as the core might be the key ceRNA mechanism affecting the progression of thyroid cancer.A relevant PPI network was constructed based on the DEmRNA contained in the NCceRNA network and protein complex modules that could affect tumor cell cycle and cell proliferation as well as tumor migration and invasion were identified.Potential pathway interaction mechanisms have been explored based on reported disease genes and drug targets.In addition,TF biomarkers related to immunotherapy for thyroid cancer have been mined by associating TF with TME and immune cells.In conclusion,the relevant research in this paper provides the basis and new ideas for further exploration of the clinical diagnosis and immunotherapy of thyroid cancer. |
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