Identification of novel genes and pathways in colorectal cancer exosomes: a bioinformatics study

Abstract

Background: Colorectal cancer (CRC) is a major public health problem, being the leading causes of mortality and morbidity worldwide. Exosomes are crucial to the molecular pathogenesis of CRC. It is essential to investigate the key differentially expressed genes (DEGs) in CRC exosomes. Methods: The DEGs between CRC patients and normal participants were screened using microarray data downloaded from the Gene Expression Omnibus (GEO) and exoRBase database. Gene ontology (GO), pathway enrichment analysis, protein-protein interaction (PPI) network, module analysis, overall survival (OS) analysis of hub genes and functional annotation of DEGs were performed. Results: A total of 149 DEGs in CRC exosomes and 1,507 DEGs in CRC tissues were identified with selecting criteria of P value <0.05. GO terms of positive regulation of gene expression, protein binding to Golgi, cellular protein metabolic process and endonuclease activity were significantly enriched in CRC exosomes. CRC exosomes were mainly enriched in pathways of RNA transport, alcoholism, viral carcinogenesis, spliceosome and Ras signaling pathway. We then selected UBC, H3F3A, HIST2H2AA3, AKT3, and HSPA1B as the hub protein in CRC exosomes according to the PPI network. OS analysis showed overexpression of HIST2H2AA3 was related to poor prognosis. Four oncogenes including H3F3A , U2AF1 , P2RY8 and APOBEC3B were identified in the exosomes. There was no significant difference in the ratio of tumor suppressor genes (TSGs) to oncogenes between tumor tissues and exosomes according to functional annotation of DEGs. Conclusions: Hub genes including UBC, H3F3A, HIST2H2AA3, AKT3 , and HSPA1B might serve as new diagnostic and therapeutic targets of CRC in the future.