Identification of key genes and pathways in seminoma by bioinformatics analysis

Background: Seminoma accounts for the most part of cases of testicular germ cell tumor, which is the most common malignancy among males between ages 15 and 44 years. Understanding the molecular mechanism of tumorigenesis is important for better clinical diagnosis and treatment. Purpose: We performed bioinformatics analysis to better understand seminoma at the genetic level and to explore potential candidate genes or molecules for diagnosis, treatment, and prognosis. Methods: A gene expression profile (GSE8607), containing 40 seminoma samples and three healthy testes samples, was analyzed to identify differentially expressed genes (DEGs) associated with the occurrence of seminoma. Functional annotation was then performed using gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. Cytoscape with Search Tool for the Retrieval of Interacting Genes was used to construct a protein-protein interaction (PPI) network of the DEGs and select hub genes. Moreover, validation of expression level and Kaplan-Meier analysis for overall survival were conducted to those hub genes. Results: A total of 1,636 DEGs were identified between seminoma and healthy samples, including 701 up-regulated in seminoma that were enriched in the regulation of immune responses, defense responses, receptor activity, and signal transducer activity; 935 were down-regulated in seminoma and were associated with reproductive processes, kinase activity, and carbohydrate derivative binding. Five hub genes were selected from the PPI network according to the degree of connectivity: IL6, VEGFA, IL10, CCR5, and CXCR4. Among them, high expression levels of CCR5 and CXCR4 were associated with poor prognosis for seminoma patients. Four modules selected from the PPI network revealed that seminoma was connected with the Janus kinase-signal transducers and activators of transcription signaling pathway, chemokine signaling pathway, endocytosis, and cytokine-cytokine receptor interaction. Conclusion: These identified DEGs and hub genes facilitate our knowledge of the underlying molecular mechanism of seminoma and have the potential to be used as diagnostic biomarkers or therapeutic targets for seminoma.