Abstract
Brain metastasis is a common complication of breast cancer (BC); however, the interaction networks and driver genes that lead to brain metastasis in BC patients are still unknown. In this study, we employed bioinformatics analyses to discover hub genes and long noncoding RNA- (lncRNA-) protein-coding gene (PCG) networks related to BC brain metastasis (BCBM). Firstly, we screened differentially expressed PCGs and lncRNAs in normal and BCBM samples using the GSE52604 dataset. Subsequently, differentially expressed genes (DEGs) and overall interaction networks were constructed, and topological degrees were analyzed to identify potential driver genes. After identifying the hub pathogenic module by weighted gene coexpression network analysis (WGCNA), the genes in the hub module were evaluated for functional enrichment. Finally, we constructed multiple interaction networks associated with BCBM and identified seven potential driver genes, out of which MYBPC1 was the only overlapping gene in the adopted analytical methods. It is worth mentioning that we validated the prognostic value of the identified hub genes in TCGA database and evaluated the prediction ability of MYBPC1 in the GSE38057 dataset. In addition, the CIBERSORT algorithm revealed changes in the immune microenvironment. In conclusion, the driver PCGs and lncRNAs in the interaction networks can be utilized as a promising therapeutic strategy for the treatment of brain metastasis in BC patients.
Highlights
Breast cancer (BC) is the most commonly diagnosed cancer in women [1]
Given the dismal prognosis associated with a BC brain metastasis (BCBM) diagnosis, knowing what motivates cancer cells to metastasize and populate the brain may be the first step toward possibly stopping metastasis and eradicating metastatic cancer cells
We explored the differential expression of protein-coding gene (PCG) and long noncoding RNAs (lncRNAs) in 35 BCBM and ten normal samples
Summary
As with other types of cancer, metastasis poses a serious challenge in the management of BC. Metastasis is the process that causes the distant spread of BC to the liver, bones, lungs, and brain. BC is the second leading cause of metastatic encephalopathy after lung cancer [2]. Brain metastases have been found to occur in 10–16% of surviving individuals with advanced BC and as high as 30% in autopsy series [3]. The brain is the primary location of BC metastases in 13% of patients [4]. Given the dismal prognosis associated with a BC brain metastasis (BCBM) diagnosis, knowing what motivates cancer cells to metastasize and populate the brain may be the first step toward possibly stopping metastasis and eradicating metastatic cancer cells
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