Distinct Clinical Impact and Biological Function of Angiopoietin and Angiopoietin-like Proteins in Human Breast Cancer

Secreted angiopoietin/angiopoietin-like ( / ) proteins are involved in many biological processes. However, the role of these proteins in human breast cancers (BCs) remains largely unclear. Here, we conducted integrated omics analyses to evaluate the clinical impact of / proteins and to elucidate their biological functions. In BCs, we identified rare mutations in / genes, frequent gains of , , and , and frequent losses of , , and , but observed that , , and were robustly downregulated in multiple datasets. The expression levels of , , and were positively correlated with overall survival (OS), while the expression levels of were negatively correlated with OS. Additionally, the expression levels of and were positively correlated with distant metastasis-free survival (DMFS), while the expression levels of and were negatively correlated with DMFS. The prognostic impacts of / genes depended on the molecular subtypes and on clinical factors. We discovered that various / genes were co-expressed with various genes involved in different pathways. Finally, with the exception of , the remaining genes showed significant correlations with cancer-associated fibroblasts, endothelial cells, and microenvironment score, whereas only was significantly correlated with immune score. Our findings provide strong evidence for the distinct clinical impact and biological function of / proteins, but the question of whether some of them could be potential therapeutic targets still needs further investigation in BCs.