Profiling and integrated analysis of differentially expressed circRNAs as novel biomarkers for breast cancer

Breast cancer (BC) is a globally common cancer with the highest and increasing morbidity and mortality among females. Novel biomarkers are warranted to be discovered for the early detection, treatment, and prognosis of BC. In this study, we investigated the profiles of differentially expressed (DE) circular RNAs (circRNAs) by competing endogenous RNAs (ceRNA) microarray to construct a genome-wide circRNA profile. Then, we performed Gene Ontology (GO) analysis and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analysis of the host genes (HGs) of circRNAs. A total of 4, 370 DE circRNAs were detected and GO and KEGG analysis showed that they were significantly associated with cell cycle, DNA replication, BC, and familial BC. We validated the differential circRNAs and relevant HGs through quantitative real-time polymerase chain reaction and constructed a putative circRNA-microRNA-messenger RNA regulatory network. Eight circRNAs, including hsacirc₀069094, hsacirc₀062558, hsacirc₀074026, hsacirc₀079876, hsacirc₀017536, hsacirc₀023302, hsacirc₀017650, and hsacirc₀017545, were validated significantly DE in BC tissue and associated with TNM staging, lymph node infiltration, and Ki67. Hsacirc₀069094, hsacirc₀079876, hsacirc₀017650, and hsacirc₀017526 were upregulated in plasma. This study revealed the general expression characteristics of specific DE circRNAs in BC and hsacirc₀069094, hsacirc₀079876, hsacirc₀017650, and hsacirc₀017526 might be promising candidate targets.