Background: Hypopharyngeal and esophageal squamous cell carcinoma (ESCC) are the most common double primary tumors with poor prognosis. Intensive work has been made to illuminate the etiology, but the common carcinogenic mechanism remains unclear. Thus, we conducted the study to seek to find the common gene signatures and key functional pathways associated with oncogenesis and treatment in hypopharyngeal squamous cell carcinoma (HSCC) and ESCC by bioinformatic analysis. Methods: Three independent datasets (GSE2379, GSE20347, and GSE75241) were screened out from the Gene Expression Omnibus (GEO) database and the overlapping differentially expressed genes (DEGs) were identified using GEO2R online platform. Subsequently, the Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analysis of DEGs were conducted using database for annotation, visualization and integrated discovery (DAVID). Meanwhile, the protein–protein interaction network (PPI) constructed by search tool for the retrieval of interacting genes (STRING) was visualized using Cytoscape. Afterwards, the most key module and hub genes were extracted from the PPI network using the Molecular Complex Detection plugin. Moreover, the gene expression profiling interactive analysis (GEPIA) was applied to verify the expression differences and conduct the survival analyses of hub genes. Finally, the interaction network of miRNAs and hub genes constructed by encyclopedia of RNA interactomes (ENCORI) was visualized using Cytoscape. Results: A total of 43 DEGs were identified, comprising 25 upregulated genes and 18 downregulated genes, which were mainly involved in the extracellular matrix-receptor interaction, collagen metabolic, epidermis development, cell adhesion, and PI3K/Akt signaling pathways. Subsequently, 12 hub genes were obtained and survival analysis demonstrated SERPINE1 and SPP1 were closely related to poor prognosis of patients with HSCC and ESCC. Finally, hsa-miR-29c-3p, hsa-miR-29a-3p, and hsa-miR-29b-3p were confirmed as the top 3 interactive miRNAs that target the most hub genes according to the interaction network of miRNAs and hub genes. Conclusion: The common gene signatures and functional pathways identified in the study may contribute to understanding the molecular mechanisms involved in the carcinogenesis and progression of HSCC and ESCC, and provide potential diagnostic and therapeutic targets.
Background: In osteosarcoma, the lung is the most common metastatic organ. Intensive work has been made to illuminate the pathogeny, but the specific metastatic mechanism remains unclear. Thus, we conducted the study to seek to find the key genes and critical functional pathways associated with progression and treatment in osteosarcoma with lung metastasis.Methods: Two independent datasets (GSE14359 and GSE85537) were screened out from the Gene Expression Omnibus (GEO) database and the overlapping differentially expressed genes (DEGs) were identified using GEO2R online platform. Subsequently, the Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analysis of DEGs were conducted using DAVID. Meanwhile, the protein-protein interaction (PPI) network constructed by STRING was visualized using Cytoscape. Afterwards, the key module and hub genes were extracted from the PPI network using the MCODE and cytoHubba plugin. Moreover, the raw data obtained from GSE73166 and GSE21257 was applied to verify the expression differences and conduct the survival analyses of hub genes, respectively. Finally, the interaction network of miRNAs and hub genes constructed by ENCORI was visualized using Cytoscape.Results: A total of 364 DEGs were identified, comprising 96 downregulated genes and 268 upregulated genes, which were mainly involved in cancer-associated pathways, adherens junction, ECM-receptor interaction, focal adhesion, MAPK signaling pathway. Subsequently, 10 hub genes were obtained and survival analysis demonstrated SKP2 and ASPM were closely related to poor prognosis of patients with osteosarcoma. Finally, hsa-miR-340-5p were found to be most closely associated with these hub genes according to the interaction network of miRNAs and hub genes.Conclusion: The key genes and functional pathways identified in the study may contribute to understanding the molecular mechanisms involved in the carcinogenesis and progression of osteosarcoma with lung metastasis, and provide potential diagnostic and therapeutic targets.
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