The Overexpression of CD80 and ISG15 Are Associated with the Progression and Metastasis of Breast Cancer by a Meta-Analysis Integrating Three Microarray Datasets

摘要

Breast cancer is a common cancer and could result in a substantial mortality. The study aimed to screen gene signatures associated with the development and metastasis of breast cancer and explore their regulation mechanisms. Three datasets of GSE10797, GSE8977 and GSE3744 were downloaded from GEO (Gene Expression Omnibus) database, containing 55 breast cancer samples and 27 normal samples. After data preprocessing using limma software and RMA (robust multi-array average) algorithm, DEGs (differentially expressed genes) between breast tumor and normal tissues in three individual experiments were identified using MADAM package. Function and pathway enrichment analyses were performed for the DEGs. Transcription factors and TAGs (tumor associated genes) among the DEGs were recognized and the PPI (protein-protein-interaction) network for the DEGs was constructed using Cytoscape software. The mRNA expression was analyzed via real-time quantitative PCR and protein expression was measured by western blotting. Totally, 100 DEGs were identified, including 33 up-regulated genes and 67 down-regulated genes. Among them, up-regulated DEGs such as CD80 was enriched in toll-like receptor (TLR) interaction pathway and the TAG, ISG15 was related to RIG-I-like receptor signaling pathway, while CXCL10 was involved in both of the two pathways. Whereas, the down-regulated DEG, CXCL12 was significantly associated with axon guidance pathway. Additionally, these DEGs were also pivotal nodes in the PPI network with high degrees. Besides, CXCL10 and CD80 were both interacted with IFNG. The mRNA expression of ISG15 was obviously enhanced in human breast cancer cells MCF-7, while no significant difference of CXCL10 mRNA level was found between MCF10A and MCF-7 cells. Moreover, the proteins expression levels of CD80 and ISG15 were significantly increased in MCF-7, MDA-MB-468 and MDA-MB-231 breast cancer cells than in normal MCF10A cells. CD80 might be responsible for the breast cancer's progression and metastasis via regulating innate immune system. In addition, ISG15 is identified as a crucial gene signature associated with breast cancer development and metastasis via RIG-I-like receptor signaling pathway.