Identification of key molecular pathways and genes in BRCA1 and BRCA2-mutant ovarian cancer: evidence from bioinformatics analysis

Aeshah A. Awaji; Abdulkadir Yusif Maigoro; Abdullahi Tunde Aborode; Ashraf Akintayo Akintola; Dorcas Oladayo Fatoba; Einass Babikir Idris; Abeer Babiker Idris; Saman Jafri; Ekram Shoaib; Isreal Ayobami Onifade; Zainab Olapade; Modupe Oladayo; Ifeyinwa Anne Ihemegbulem; Oluwaseun Ipede; Abidemi Ruth Idowu; Funke V. Alabi; Ibude Jane Aruorivwooghene; Oghenetanure Ryan Enaworu; Abdullahi Jamiu; Adetolase A. Bakre; Hyung Wook Kwon; Ui Wook Hwang; Ridwan Olamilekan Adesola

doi:10.1007/s42764-024-00133-9

Genome Instability & Disease ›› 2024, Vol. 5 ›› Issue (4) : 164-182. DOI: 10.1007/s42764-024-00133-9

Original Research Paper

Identification of key molecular pathways and genes in BRCA1 and BRCA2-mutant ovarian cancer: evidence from bioinformatics analysis

Author information +

¹Department of Biology, Faculty of Science, University College of Taymaa, University of Tabuk, 71491, Tabuk, Saudi Arabia

²NOBLEKINMAT Ltd. Bioinformatics Research Group, Ibadan, Nigeria

³Department of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Seoul, South Korea

⁴Convergence Research Center for Insect Vector, Incheon National University, Seoul, South Korea

⁵Department of Chemistry, Mississippi State University, 39759, Starkville, MS, USA

⁶School of Industrial Technology Advances, Kyungpook National University, 41566, Daegu, Republic of Korea

⁷Department of Medical Microbiology, Rashid Complex Medical Clinics, Riyadh, Saudi Arabia

⁸Institute of Natural and Applied Sciences, Erciyes University, Kayseri, Turkey

⁹Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, India

¹⁰Clinical Laboratory Sciences Department, College of Applied Medical Sciences, University of Hafr Al-Batin, Hafr Al-Batin, Saudi Arabia

¹¹Department of Biology, University at Albany, Albany, NY, USA

¹²Department of Biology, Lamar University, Beaumont, USA

¹³Department of Chemistry and Biochemistry, Central Washington University, Ellensburg, USA

¹⁴Department of Pharmacy, University of Jos, Jos, Nigeria

¹⁵School of Earth, Environment, and Sustainability, Georgia Southern University, Statesboro, USA

¹⁶Department of Microbiology and Immunology, School of Medicine, University of Louisville, Louisville, KY, USA

¹⁷Department of Biomedical Informatics, Nova Southeastern University, Fort Lauderdale, USA

¹⁸Department of Dietetics and Nutrition, Medical Center, University of Kansas, Kansas City, KS, USA

¹⁹Department of Advanced Studies in Clinical Research, University of California San Diego, La Jolla, CA, USA

²⁰Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, 24060, Blacksburg, VA, USA

²¹Department of Veterinary Medicine, Faculty of Medicine, University of Ibadan, Ibadan, Nigeria

²²Department of Biology, Teachers College and Institute for Phylogenomics and Evolution, Kyungpook National University, 41566, Daegu, Republic of Korea

²³Institute for Korean Herb-Bio Convergence Promotion, Kyungpook National University, 41566, Daegu, Republic of Korea

²⁴Phylomics Inc., 41910, Daegu, Republic of Korea

²⁵The University of Tennessee Health Science Center (UTHSC), Memphis, TN, USA

²⁶Health Research Incorporated, New York, NY, USA

²⁷Noblekinmat Research Group, Ibadan, Nigeria

^z radesola758@stu.ui.edu.ng

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Abstract

BRCA1 and BRCA2 mutations significantly increase the risk of breast and ovarian cancers (OC) by affecting crucial cellular processes such as cell cycle regulation, DNA repair, and apoptosis. Despite understanding their broad impacts, the detailed effects on gene expression and signaling pathways in OC remain unclear. This study aims to elucidate these dynamics by analyzing RNA-Seq data from 24 OC patients with BRCA1/2 mutations and controls using advanced molecular techniques. Differential expression analysis identified 6136 DEGs in BRCA1-mutant and 3615 DEGs in BRCA2-mutant OCs, with 2041 overlapping DEGs. These shared genes underwent Gene Ontology (GO), KEGG, and Protein–protein interaction (PPI) network analyses, revealing pathways like MyD88-independent TLR signaling and mRNA vaccine activation of dendritic cells. Key genes (TRAF3, TICAM1, IRF7, CD40, IRF3, SARM1, RAB11FIP, and PRKCE) involved in TRIF-dependent TLR signaling showed distinct expression patterns in BRCA1/2-deficient OCs. The top 10 hub genes identified were evaluated for their prognostic significance using the Kaplan–Meier Plotter database. The findings highlight the genetic landscape and pathways altered by BRCA1/2 mutations in OC, offering insights for improved diagnostics and personalized treatments. Additionally, the impact on immunosurveillance through the TRIF-dependent TLR system suggests new immunotherapeutic strategies for OC patients with BRCA1/2 mutations, addressing the challenge of cancer recurrence.

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Aeshah A. Awaji, Abdulkadir Yusif Maigoro, Abdullahi Tunde Aborode, Ashraf Akintayo Akintola, Dorcas Oladayo Fatoba, Einass Babikir Idris, Abeer Babiker Idris, Saman Jafri, Ekram Shoaib, Isreal Ayobami Onifade, Zainab Olapade, Modupe Oladayo, Ifeyinwa Anne Ihemegbulem, Oluwaseun Ipede, Abidemi Ruth Idowu, Funke V. Alabi, Ibude Jane Aruorivwooghene, Oghenetanure Ryan Enaworu, Abdullahi Jamiu, Adetolase A. Bakre, Hyung Wook Kwon, Ui Wook Hwang, Ridwan Olamilekan Adesola. Identification of key molecular pathways and genes in BRCA1 and BRCA2-mutant ovarian cancer: evidence from bioinformatics analysis. Genome Instability & Disease, 2024, 5(4): 164‒182 https://doi.org/10.1007/s42764-024-00133-9