Determination of Genetic and Epigenetic Modifications-Related Prognostic Biomarkers of Breast Cancer: Genome...

The high heterogeneity of breast cancer (BRCA) makes it more challenging to interpret the genetic variation mechanisms involved in BRCA pathogenesis and prognosis. Areas with high DNA methylation (such as CpG islands) were accompanied by copy number variation (CNV), and these genomic variations affected the level of DNA methylation. In this study, we characterized intertumor heterogeneity and analyzed the effects of CNV on DNA methylation and gene expression. In addition, we performed a Genetic Set Enrichment Analysis (GSEA) to identify key pathways for changes between patients with low and high expression of genes. Our analysis found two key genes, namely, HPDL and SOX17. The protein expressed by HPDL is 4-hydroxyphenylpyruvate dioxygenase-like protein, which has dioxygenase activity. SOX17 is a transcription factor that can inhibit Wnt signaling, promote the degradation of activated CTNNB1, and participate in cell proliferation. Our analysis found that the CNV of HPDL and SOX17 is not only related to the patient's prognosis, but also related to gene methylation and expression levels affecting the patient's survival time. Among them, the high-methylation, low-expression HPDL and SOX17 showed poor prognosis. And the addition of two copies of SOX17 is associated with a lower survival rate, while a decrease in the copy number of HPDL also suggests a poor prognosis. This study provided an effective bioinformatics basis for further exploration of molecular mechanisms related to BRCA and assessment of patient prognosis, but the development of biomarkers for diagnosis and treatment still requires further clinical data validation.