Promoter Methylation-Regulated Differentially Expressed Genes in Breast Cancer

Samar Sindi; Norah Hamdi; Sabah Hassan; Magdah Ganash; Mona Alharbi; Najla Alburae; Sheren Azhari; Shadi Alkhayyat; Ayman Linjawi; Heba Alkhatabi; Aisha Elaimi; Ghadeer Alrefaei; Nouf Alsubhi; Aziza Alrafiah; Safiah Alhazmi

doi:10.2147/BCTT.S408711

Promoter Methylation-Regulated Differentially Expressed Genes in Breast Cancer

Breast Cancer (Dove Med Press). 2023 Jul 6:15:435-450. doi: 10.2147/BCTT.S408711. eCollection 2023.

Authors

Samar Sindi^#¹, Norah Hamdi^#^{1

2}, Sabah Hassan^{1

3}, Magdah Ganash¹, Mona Alharbi¹, Najla Alburae¹, Sheren Azhari¹, Shadi Alkhayyat⁴, Ayman Linjawi⁵, Heba Alkhatabi^{6

7}, Aisha Elaimi^{7

8}, Ghadeer Alrefaei⁹, Nouf Alsubhi¹⁰, Aziza Alrafiah⁷, Safiah Alhazmi^{1

3}

Affiliations

¹ Department of Biological Sciences, King Abdulaziz University, Jeddah, Saudi Arabia.
² Department of Biology, King Khalid University, Abha, Saudi Arabia.
³ Princess Dr. Najla Bint Saud Al-Saud Center for Excellence Research in Biotechnology, King Abdulaziz University, Jeddah, Saudi Arabia.
⁴ Department of Internal Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
⁵ Medical Reference Clinics, Jeddah, Saudi Arabia.
⁶ Hematology Research Unit (HRU), King Fahad Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.
⁷ Department of Medical Laboratory Science, King Abdulaziz University, Jeddah, Saudi Arabia.
⁸ Centre of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia.
⁹ Department of Biology, University of Jeddah, Jeddah, Saudi Arabia.
¹⁰ Biological Sciences Department, College of Science & Arts, King Abdulaziz University, Rabigh, Saudi Arabia.

^# Contributed equally.

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: DNA methylation; biomarker; breast cancer; differentially expressed gene; differentially methylated regions; whole-genome bisulfite sequencing.

Grants and 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.