Informatics Approaches to Identify Potential Biomarkers for Breast Cancer Therapeutic Targets Using Microarray Data
Breast Cancer (BC) is characterized by aberrant genetic and epigenetic alterations, necessitating a systems biology approach to determine its complexity. This study integrated microarray datasets (GSE45827 and GSE20685) from 506 samples (253 tumors, 253 normal) to identify 38,272 genes, including 9823 protein-coding, 14,512 noncoding RNAs (ncRNAs) and 13,937 long intergenic noncoding RNAs (lncRNAs). After normalization and rigorous preprocessing, 519 Differentially Expressed Genes (DEGs) were identified (239 upregulated and 280 downregulated), with key hub genes (MED12, CCND1, RAD51-AS1) identified via Protein–Protein Interaction (PPI) network analysis (887 nodes, 10,398 edges) and centrality metrics (CytoHubba, CytoNCA). lncRNA-mRNA co-expression networks revealed strong correlations between LINC0043 ([Formula: see text] 0.81), LINC0055 ([Formula: see text] 0.83) and LINC0062 ([Formula: see text] 0.75) and CCND1, LINC0055 ([Formula: see text] 0.83), LINC0066 ([Formula: see text] 0.79) and LINC0076 ([Formula: see text] 0.76) and MED12, suggesting their roles as competing endogenous RNAs (ceRNAs) in modulating BC pathways. Survival analysis demonstrated the prognostic significance of MED12 (HR [Formula: see text] 0.62, [Formula: see text] > 0.003), CCND1 (HR [Formula: see text] 0.58, [Formula: see text] > 0.001) and RAD51-AS1 (HR [Formula: see text] 1.51, [Formula: see text] > 0.007) in Recurrence-Free Survival (RFS). The pan-cancer analysis highlighted the cross-cancer relevance of STAT3 ([Formula: see text] 0.66, gastric cancer) and TP53 ([Formula: see text]0.72), underscoring their potential as universal biomarkers. By employing multi-omics validation using The Cancer Genome Atlas (TCGA), the GEPIA2 datasets study bridges computational predictions with actionable biology. Our findings provide an mRNA-ceRNA network blueprint, identifying MED12-CCND1-lncRNA axes as therapeutic targets and advancing precision oncology strategies for BC management.
Authors
- Amira Metouekel (ORCID: https://orcid.org/0000-0001-8634-6974)
- Mohammed Bourhia (ORCID: https://orcid.org/0000-0003-3707-8461)
- Adil Jamal (ORCID: https://orcid.org/0000-0002-8724-5566)
- Arfa Safder (ORCID: https://orcid.org/0009-0005-4630-4303)
- Imran Zafar (ORCID: https://orcid.org/0000-0002-9246-0850)
- Samra Babar
- Khalid S. Almaary (ORCID: https://orcid.org/0009-0006-6745-8480)
- Huifen Zhou
Institutions
- Université de Technologie de Compiègne (FR)
- Quaid-i-Azam University (PK)
- University of Lahore (PK)
- King Saud University (SA)
- Université Ibn Zohr (MA)
- Hubei University of Science and Technology (CN)
- University of Faisalabad (PK)
Publication Details
- Journal
- Journal of Computational Biophysics and Chemistry
- Published
- 2025-03-28
- DOI
- https://doi.org/10.1142/s2737416525500371
- Citations
- 6
- Primary Topic
- Gene expression and cancer classification
- Type
- article
- Field-Weighted Citation Impact
- 4.84