Abstract
Breast cancer (BRCA) is a malignant tumor with a high incidence and poor prognosis in females. However, its pathogenesis remains unclear. In this study, based on bioinformatic analysis, we found that LINC00467 was highly expressed in BRCA and was associated with tumor metastasis and poor prognosis. The genomic and epigenetic analysis showed that LINC00467 may also be regulated by copy number amplification (CNA), chromatin openness, and DNA methylation. In vitro experiments showed that it could promote the proliferation, migration, and invasion of BRCA cells. Competitive endogenous RNA (ceRNA) regulatory network analysis and weighted gene coexpression network analysis (WGCNA) suggested that LINC00467 may play a role in signaling pathways of peroxisomal lipid metabolism, immunity, and others through microRNAs (miRNAs) targeting transforming growth factor beta 2 (TGFB2). In addition, copy number amplification and high expression of LINC00467 were associated with the low infiltration of CD8+ and CD4+ T cells. In conclusion, we found that LINC00467, driven by copy number amplification and DNA demethylation, may be a potential biomarker for the diagnosis and prognosis of BRCA and a tumor promoter acting as a potential therapeutic target for BRCA as well.
Highlights
Breast cancer (BRCA) is one of the most common malignancies affecting women worldwide, and approximately more than 1.3 million women will develop BRCA during their lifetime each year
Through data mining of the public databases, including Gene Expression Omnibus (GEO), the Cancer Genome Atlas (TCGA), Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), and Cancer Cell Line Encyclopedia (CCLE), we found that the LINC00467 expression rose significantly in BRCA and could be used as the potential diagnostic and prognostic biomarker for it
Patients with copy number amplification of LINC00467 had a higher proportion of advanced stages and more changes of genome fragments (Supplementary Figure. 3E-3G). These results fully indicated that genome amplification of LINC00467 may be one of the causes of upregulation of LINC00467 expression, LINC00467 may be one of the driver genes of BRCA, and its copy number amplification may be a molecular biomarker of metastasis and recurrence for BRCA patients as well
Summary
Breast cancer (BRCA) is one of the most common malignancies affecting women worldwide, and approximately more than 1.3 million women will develop BRCA during their lifetime each year. BRCA has a high mortality rate and continues to be the most common cause of death among female cancer patients in the world, causing 458,000 deaths every year [1], and its incidence continues to grow globally [2]. BRCA can be mainly divided into subtypes of luminal A, luminal B, normal breast-like, HER-2, and basal-like. The causes of BRCA are complicated, among which obesity and smoking are the most common risk factors [3, 4]. BRCA treatments include surgery, chemotherapy, hormonotherapy, radiotherapy, and immunotherapy; due to the intratumor heterogeneity in breast cancer, its pathogenesis has remained unclear. The predictive biomarker(s) for recurrence and metastasis of BRCA are still
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