Identification of An Immune-Related Biomarker Model Based on the CeRNA Network for Triple-Negative Breast Cancer

Abstract

Background Triple-negative breast cancer (TNBC) accounts for 10–20% of all breast cancer cases. It represents an aggressive malignancy of frequently high histologic grade with no effective specific targeted therapies. Numerous studies have indicated that abnormal expressions of circRNAs may be a potential mechanism for the development and progression of cancer. CircRNAs may bind with miRNAs to influence the interaction between miRNAs and mRNAs and contribute to the progression of tumors, which was called as competitive endogenous RNA (ceRNA) hypothesis. In this study, we aimed to establish the ceRNA network in TNBC, and identify immune-related genes. Methods The circRNA (GSE101123), microRNA (TCGA-TNBC), and mRNA (TCGA-TNBC) expression profiles of TNBC were collected from the GEO database and TCGA database. Immune-related genes were collected from the ImmPort database. Differentially expressed circRNAs, miRNAs and mRNAs were identified. Then, the interacting relationships among circRNA-miRNA and miRNA-mRNA were predicted, and we constructed an immune-related ceRNA network. Subsequently, an immune-related signature was developed based on mRNAs in the ceRNA network. Results A total of 24 DEcircRNAs, 45 DEmiRNAs, 4814 DEmRNAs were identified. After overlapping DEmRNAs with immune-related genes, we obtained 490 immune-related DEmRNAs (DEIRGs). Then we took the intersection of 490 DEIRGs and 407 predicted miRNAs to obtain 5 immune-related mRNAs (IRGs). GO and KEGG pathway analysis showed that IRGs were associated with immunity. Then, an immune-related ceRNA network was constructed. Among the IRGs in ceRNA network, the AUC curve indicated that ADCYAP1R1, ANGPTL2, IL2RA and TGFBR2 with significantly diagnosis value were identified. Finally, we analyzed the correlation between 4 hub genes and immune infiltrating cells, ADCYAP1R1 were negatively associated with Type 2 T helper cell. Conclusion We screened the key genes and established an immune-related ceRNA network involved in TNBC, which will assist in understanding the molecular mechanisms underlying the carcinogenesis and progression.