Epigenetic identification of LTBP4 as a putative tumor suppressor in breast cancer

<b>Aim:</b> To explore the LTBP4’s expression, prognostic significance and molecular mechanism of action in breast cancer (BC). <b>Methods:</b> On the basis of omics datasets and experiments, we conducted a synthetical analysis of LTBP4 in BC. <b>Results &amp; conclusion:</b> LTBP4 was downregulated in BC with high promoter methylation and low genetic alteration. DNA methylation was negatively associated with LTBP4 mRNA expression. Higher LTBP4 associated with better survival. LTBP4 was enrichment in extracellular matrix receptor interactions, cell adhesion molecules, cell cycle and MAPK pathway. LTBP4 expression and methylation were positively and negatively associated with tumor infiltrating immune cells, respectively. In conclusion, LTBP4 is a putative tumor suppressor in BC, which expression is regulated by DNA methylation and relates with prognosis. We evaluated the mRNA and protein expression profiles of LTBP4 using multiple datasets and we found LTBP4 was downregulated in breast cancer (BC) tissues and cell lines. Genetic and epigenetic analysis revealed frequently promoter methylation of LTBP4 in BC tissues and cell lines. The high LTBP4 expression was significantly associated with better survival in BC and correlated with clinical pathological parameters. Based on bioinformatic tools, we found LTBP4 may be involved in cell cycle, MAPK pathway and the tumor immune microenvironment.