Understand the role of exosomal miRNA in the development of breast cancer in patients with chronic HBV infection

Abstract

Background: Female chronic hepatitis B patients has shown a higher incidence of breast cancer with poorer prognosis, compared to the non-infected female patients. A significant difference in miRNAs expression in serum exosomes has been identified between female patients with chronic HBV infection and non-infected female. Whether this difference could contribute to the differential incidence and development of breast cancer in these female patients has not been fully understood.Methods: Information of exosomal expression of miRNAs (expression profiles of GSE33857) were acquired from the Gene Expression Omnibus (GEO) database. Targeted genes of this miRNAs and the differentially expressed genes of breast cancer in GEPIA V2.0 database was used to obtain the differentially expressed genes (DEGs). Four analytic methods were performed, including functional annotation, protein-protein interaction (PPI) network and module construction, the clinical pathologic parameters analysis, alongsides prognosis analysis.Results: In the serum exsomes, expression of miR-1237-3p and miR-363-3p were down-regulated whilst expression of miR-100-5p, miR-125b-5p, miR-1260a, miR-1287-5p, miR-148a-3p, miR-885-5p and miR-99a-5p were up-regulated in female chronic hepatitis B (CHB) patients. 228 up-regulated genes and 641 down-regulated genes were selected as DEGs. The DEGs involved in several biological processes ranging from cellular response to hormone stimulus. According to the main enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway was the pathways in cancer. Our analysis revealed that among the hub genes, CXCL11 was up-regulated and CXCL12, GNG2, LPAR1, GPR17, CXCL1, ADCY5, ADCY3, CX3CL1, S1PR1 were down-regulated. These genes expression levels were verified in UALCAN, Oncomine and HPA database. High expression level of CXCL11 and low expression levels of CXCL12, LPAR1, ADCY3 and CX3CL1 were positively correlated with some clinical pathological parameters that predicted worse prognosis. Kaplan-Meier (K-M) plotter analysis revealed that these genes that showed a low expression level were positively correlated with poor prognosis of breast cancer, and the high expression genes were negatively correlated with poor prognosis of breast cancer.Conclusion: This bioinformatics analysis study explored the mechanisms of chronic HBV related occurrence and development of breast cancer by changing the expression of miRNAs of serum exosomes. It provided novel directions and therapeutic strategy for chronic HBV infection associated occurrence and development of breast cancer in female patients.