Bioinformatic Investigation of Genetic Changes in Paraoxonase Genes in Breast Cancer and Breast Cancer Subtypes

Abstract

Objective: Among women, breast cancer (BC) is the most prevalent form of cancer. Many molecular targets have been discovered for BC prognosis and treatment. However, new markers still need to be identified, as cancer pathogenesis is triggered by different mechanisms. The aim of this study was to examine the changes in the paraoxonase genes (PON1, PON2, and PON 3) involved in the pathogenesis of BC. Materials and Methods: The characteristics of the mutations were evaluated with the Cbioportal database. Kaplan-Meier Plot evaluated recurrence-free survival (RFS). The UALCAN database determined the promoter methylation. Gene expression was evaluated by GEPIA2.0 database. Results: PON1 harbored the most mutations. There was a significant decrease in PON3 expression levels in BC samples compared with healthy samples. PON1 and PON2 expression levels did not differ between BC tissue and normal adjacent tissue. Elevated expression levels of PON1 and PON2 genes were correlated with longer RFS, whereas reduced expression of the PON2 gene showed an association with longer RFS. Moreover, the promoter regions of PON1 and PON 3 were found to be hypermethylated, while the promoter region of PON 2 was found to be hypomethylated. The PON3 promoter region was significantly hypermethylated in luminal and human epidermal growth factor receptor 2 (HER2) + BC subtypes. However, the PON3 promoter region was significantly hypomethylated in the triple negative breast cancer (TNBC) subtype. Conclusion: These results suggest that methylation and expression status of PON3 in BC and BC subtypes (TNBC, luminal and HER2) may indicate a poor prognosis. The PON3 gene could be a negative prognostic marker in BC. However, the results should be supported by prospective studies.

Keywords

• breast cancer
• paraoxonase
• bioinformatics