Background: Triple-negative breast cancer (TNBC) is the most common and aggressive type of breast cancer with an unfavourable outcome worldwide. Novel therapeutic targets are urgently required to explore this malignancy. This study explored the ceRNA network and the important genes for predicting the therapeutic targets.
Methods: It identified the differentially expressed genes of mRNAs, lncRNAs and miRNAs between TNBC and non-TNBC samples in four cohorts (TCGA, GSE38959, GSE45827 and GSE65194) to explore the novel therapeutic targets for TNBC. Downstream analyses, including functional enrichment analysis, ceRNA network, protein–protein interaction and survival analysis, were then conducted by bioinformatics analysis. Finally, the potential core protein of the ceRNA network in TNBC was validated by immunohistochemistry.
Results: A total of 1,045 lncRNAs and 28 miRNAs were differentially expressed in the TCGA TNBC samples, and the intersections of 282 mRNAs (176 upregulations and 106 downregulations) between the GEO and TCGA databases were identified. A ceRNA network composed of 7 lncRNAs, 62 mRNAs, 12 miRNAs and 244 edges specific to TNBC was established. The functional assay showed dysregulated genes, and GO, DO and KEGG enrichment analysis were performed. Survival analysis showed that mRNA LIFR  and lncRNA AC124312.3  were significantly correlated with the overall survival of patients with TNBC in the TCGA databases (P < 0.05). Finally, the LIFR  protein was validated, and immunohistochemical results showed the upregulated expression of LIFR  in TNBC tissues.
Conclusion: Thus, our study presents an enhanced understanding of the ceRNA network in TNBC, where the key gene LIFR may be a new promising potential therapeutic target for patients with TNBC.
Keywords: triple-negative breast cancer, ceRNA network, overall survival, novel biomarkers, leukemia inhibitory factor receptor