Promoter Methylation-Regulated Differentially Expressed Genes in Breast Cancer

Abstract

Background

Breast cancer is one of the most common malignancies among women. Recent studies revealed that differentially methylated regions (DMRs) are implicated in regulating gene expression. The goal of this research was to determine which genes and pathways are dysregulated in breast cancer when their promoters are methylated in an abnormal way, leading to differential expression. Whole-genome bisulfite sequencing was applied to analyze DMRs for eight peripheral blood samples collected from five Saudi females diagnosed with stages I and II of breast cancer aligned with three normal females. Three of those patients and three normal samples were used to determine differentially expressed genes (DEG) using Illumina platform NovaSeq PE150.

Results

Based on ontology (GO) and KEGG pathways, the analysis indicated that DMGs and DEG are closely related to associated processes, such as ubiquitin-protein transferase activity, ubiquitin-mediated proteolysis, and oxidative phosphorylation. The findings indicated a potentially significant association between global hypomethylation and breast cancer in Saudi patients. Our results revealed 81 differentially promoter-methylated and expressed genes. The most significant differentially methylated and expressed genes found in gene ontology (GO) are pumilio RNA binding family member 1 (PUM1) and zinc finger AN1-type containing 2B (ZFAND2B) also known as (AIRAPL).

Conclusion

The essential outcomes of this study suggested that aberrant hypermethylation at crucial genes that have significant parts in the molecular pathways of breast cancer could be used as a potential prognostic biomarker for breast cancer.

Keywords:

• breast cancer
• DNA methylation
• biomarker
• differentially methylated regions
• differentially expressed gene
• whole-genome bisulfite sequencing

Participation Approval and Ethical Approval

The investigation was conducted in accordance with the declaration of Helsinki and was approved by the King Abdulaziz University biomedical ethics unit’s ethics committee (No.349-21). The participants signed informed consent forms.

Acknowledgments

The authors wish to express gratitude to the Central Laboratory for Biological Sciences at the Science College at King Abdulaziz University for providing advice and support.

Disclosure

The authors report no conflicts of interest in this work.

Additional information

Funding

This research work was funded by Institutional Fund Projects under grant no. (IFPHI-096-247-2020). Therefore, the authors gratefully acknowledge technical and financial support from the Ministry of Education and King Abdulaziz University, DSR, Jeddah, Saudi Arabia.