Dysregulated ceRNA network modulated by copy number variation-driven lncRNAs in breast cancer: A comprehensive analysis.

Abstract

Breast cancer is a malignancy harmful to physical and mental health in women, with quite high mortality. Copy number variations (CNVs) are vital factors affecting the progression of breast cancer. Detecting CNV in breast cancer to predict the prognosis of patients has become a promising accurate treatment in recent years. The differential analysis was performed on CNV of lncRNAs as well as the expression of lncRNAs, miRNAs and mRNAs in the normal tissue and breast tumor tissue based on The Cancer Genome Atlas (TCGA) database. And the CNV-driven lncRNAs were identified by Kruskal-Wallis test. Meanwhile, a competitive endogenous RNA (ceRNA) network regulated by CNV-driven lncRNA was constructed. As the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed, the mRNAs in the dysregulated ceRNA network were mainly enriched in the biological functions and signaling pathways including Focal Adhesion-PI3K-Akt-mTOR-signaling pathway, Neuronal System, Metapathway biotransformation Phase I and II and blood circulation, etc. The relationship between CNVs of 5 lncRNAs and their gene expression in the ceRNA network was analyzed via Chi-square test, which confirmed that except LINC00243, the expression of 4 lncRNAs was notably correlated with CNVs. The survival analysis revealed that only copy number gain of LINC00536 was evidently related to poor prognosis of patients. CIBERSORT algorithm showed that 5 lncRNAs were correlated with the abundance of immune cell infiltration and immune checkpoints. In a word, by analyzing CNV-driven lncRNAs and the ceRNA network regulated by these lncRNAs, this study explored the mechanism of breast cancer and provided novel insights into new biomarkers.