Identification of novel genetic etiology and key molecular pathways for seminoma via network-based studies

Seminoma is the most common testicular malignant germ cell tumor which severely threaten male reproductive health. However, the pathogenesis and progression mechanisms are still unclear and little research is carried out to uncover the mechanism of this cancer. To identify gene signatures that are expected to converge on particular molecular pathways may drive the development of the core cancer characteristics in seminoma. We downloaded the gene expression profiles GSE18155 from GEO database and obtained the differentially expressed genes (DEGs). Then, we performed Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses via DAVID. In total, 3,502 DEGs were identified, including 1,563 upregulated genes and 1,939 downregulated genes. The top 10 hub genes, Ubc, Ubb, Mapk8, Ar, Pten, Cdk2, Cdk4, Rac1, Top2a and Cdkn1a were identified from the protein protein interaction (PPI) network which was constructed by Cytoscape. Sub-networks analyzed by MCODE plugin revealed these genes were involved in significant molecular pathways, including ERBB2 signaling pathway, pathways in cancer, PI3K-AKT signaling pathway and cell cycle. Finally, validation of hub genes was checked via reverse transcription-polymerase chain reaction (RT-PCR) assay and immunohistochemistry (IHC). In conclusion, our study revealed that the identified hub genes increased the understanding of genetic etiology and molecular mechanisms underlying the development of seminoma, in return, they could be used as potential diagnostic biomarkers and therapeutic molecular targets for seminoma.