ORIGINAL RESEARCH article
Front. Med.
Sec. Translational Medicine
Volume 12 - 2025 | doi: 10.3389/fmed.2025.1572500
This article is part of the Research TopicThe Application of Multi-omics Analysis in Translational MedicineView all 6 articles
Multi-Omics Insights into Biomarkers of Breast Cancer Associated Diabetes -A Computational Approach
Provisionally accepted
- School of Biosciences and Technology/Medical Biotechnology Division, VIT University, Vellore, TamilNadu, India
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Introduction:Breast cancer (BC) and diabetes are multifaceted diseases with interconnected molecular mechanisms that are not yet fully elucidated. These diseases share common risk factors, biological pathways, and treatment outcomes. Methods:This study utilizes an integrative computational approach to investigate the interplay between BC and diabetes in African American (AA) and European American (EA) cohorts. It employs transcriptomic and exomic analyses to identify shared pathways and potential therapeutic targets. Results:The pooled cohort of differential expression analysis identified 2815 genes differentially expressed in BC patients with diabetes compared to those without diabetes, including 1824 upregulated and 990 downregulated genes. We reanalyzed transcriptomic data by stratifying BC patients with and without diabetes into two cohorts, identifying 3,245 DEGs in AA and 3,208 DEGs in EA, with 786 genes commonly altered between both groups. Whole-exome sequencing (WES) of 23 BC patients with diabetes revealed 899 variants across 208 unique genes, predominantly missense mutations. Among these, nine key genes were prioritized, with TNFRSF1B (L264P) and PDPN (A105G) identified as the most deleterious variants. Functional enrichment analyses highlighted the significant involvement of pathways related to extracellular matrix organization, angiogenesis, immune regulation, and signaling processes critical to cancer progression and metabolic dysfunction. The TNF pathway emerged as a central link connecting chronic inflammation, insulin resistance, and tumor growth. TNF-mediated mechanisms, including NF-κB activation, oxidative stress, and epithelial-to-mesenchymal transition (EMT), were found to drive both diseases, promoting tumorigenesis, immune evasion, and metabolic dysregulation. Conclusion:This study provides critical molecular insights into the shared mechanisms of BC and diabetes, identifying the TNF pathway as a key therapeutic target to improve outcomes for patients with these interconnected conditions.
Keywords: breast cancer, diabetes, Transcriptomics, Exome analysis and TNF pathway, Bioinforamtics
Received: 07 Feb 2025; Accepted: 12 May 2025.
Copyright: © 2025 L and C. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: George Priya Doss C, School of Biosciences and Technology/Medical Biotechnology Division, VIT University, Vellore, 632014, TamilNadu, India
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