Breast cancer (BC) is one of the most prevalent and complex diseases affecting women worldwide, significantly on the rise among Saudi females. Recent research sheds new light on the ANGPT1 gene, pointing to its prognostic impact linked to aberrant DNA methylation, which may open doors for new therapeutic approaches.
Breast cancer's increasing incidence, now representing 29.7% of all cancer cases among women in Saudi Arabia, calls for effective prognostic markers to predict outcomes and tailor treatment. DNA methylation is increasingly recognized as a key player, with its alterations frequently associated with cancer progression. A study led by researchers from King Abdulaziz University and other institutions aimed to investigate the relationship between ANGPT1 expression and DNA methylation among breast cancer patients.
Using blood samples from 49 Saudi women, 28 diagnosed with BC, the study employed whole genome bisulfite sequencing to identify novel methylation targets. Through extensive analysis of public datasets, including the METABRIC and TCGA, researchers found hypomethylation of ANGPT1 linked to elevated gene expression levels.
ANGPT1, part of the angiopoietin family responsible for regulating blood vessels, is identified as both oncogenic and negatively prognostic for breast cancer patients. The study revealed high ANGPT1 expression correlated with poor breast cancer-specific survival (BCSS). Specifically, patients exhibiting elevated ANGPT1 mRNA expression had diminished chances of survival, highlighting the gene's relevance as a biomarker.
To establish the functional significance of DNA methylation on ANGPT1 expression, the demethylation agent 5-aza-2'-deoxycytidine was applied in vitro. Results showed significant increases in ANGPT1 expression post-demethylation, confirming the hypothesis of its role being regulated by methylation changes.
Further analysis employed quantitative PCR, validating the presence of hypomethylation and its association with the level of ANGPT1 expression, supporting previously reported findings. The data indicated ANGPT1 acts not only as a marker for breast cancer prognosis but also influences tumor progression through its involvement with angiogenesis — the formation, growth and the spread of blood vessels within tumors.
This multifaceted study offers a significant gain for breast cancer research, establishing the ANGPT1 gene as a potential agent influencing prognosis and opening avenues for targeted therapies. Future research is recommended to clarify the underlying mechanisms of ANGPT1's aberrant regulation by focusing on specific methylation patterns and its interactions within the tumor microenvironment.