Objective: To seek potential metastatic tumor markers in esophageal squamous cell carcinoma (ESCC) by bioinformatics.
Methods: Four datasets (GSE70409, GSE26886, GSE161533, GSE17351) were downloaded from GEO database, and the differential expression of mRNA was screened by Limma software package. Gene ontology function and kyoto encyclopedia of genes and genomes pathway enrichment analysis were performed using the database for annotation; Protein–protein interaction network of these DEGs was constructed based on STRING database; then, the hub gene were identified by six algorithms of Cytoscape software. Using GEPIA2 database and OncoLnc database to analyze the survival of hub genes. Immune infiltration was analyzed by TIMER2 database and CIBERSORT deconvolution method.
Results: A total of 244 differentially expressed genes(DEGs)were screened from 4 data sets of GEO database, including 164 up-regulated genes and 80 down-regulated genes, which were mainly enriched at extracellular region and extracellular space, and involved in biological processes such as cell adhesion and proteolysis related to tumor invasion and metastasis. KEGG results showed that DEGs were mainly enriched in PI3K-Akt signal pathway and extracellular matrix (ECM) receptor interaction signal pathway. Through the protein interaction analysis of DEGs, we found that three hub genes (CXCL8, MMP9 and MMP13) were highly expressed in ESCC. However, the GEPIA2 database shows that only CXCL8 is associated with the overall survival of ESCC patients. The results of immune infiltration showed that macrophages and resting dendritic cells increased significantly, while mast cells and monocytes decreased significantly.
Conclusion: Three hub genes and immune infiltrating cells may play an important role in ESCC, and are expected to become potential tumor markers of ESCC and be used in the diagnosis and treatment of ESCC.