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Network Biology, 2026, 16(2): 82-102
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Article

Convergent transcriptomic signatures reveal cell cycle and DNA repair dependencies in triple-negative breast cancer: A network-based multi-dataset analysis

Chaitanya Kumar1, Ravi Verma2, Ashok Sharma3, Vishnupriya Veeraraghavan1
1Center of Molecular Medicine and Diagnostics, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences (SIMATS), Saveetha University, Chennai 600077, Tamil Nadu, India
2School of Biotechnology, Jawaharlal Nehru University, New Delhi 110067, India
3Department of Biochemistry, All India Institute of Medical Sciences, New Delhi 110029, India

Received 11 November 2025;Accepted 20 December 2025;Published online 30 December 2025;Published 1 June 2026
IAEES

Abstract
Triple-negative breast cancer (TNBC) remains one of the most aggressive and therapeutically challenging breast cancer subtypes due to the absence of hormone receptors and HER2 expression. To uncover reproducible molecular signatures and potential therapeutic targets, we performed an integrative transcriptomic analysis using three independent GEO datasets (GSE38959, GSE65216, and GSE65194). Differentially expressed genes were examined through protein-protein interaction network construction, enrichment analysis, and survival validation. A highly connected gene cluster comprising CHEK1, PLK1, AURKA, CCNA2, CCNB1, RAD51, TOP2A, KIF11, and KIF23 was consistently upregulated across datasets. These genes were predominantly involved in cell-cycle regulation and DNA-repair pathways and showed significant association with poor overall survival in TNBC cohorts. The findings suggest that dysregulation of the mitotic checkpoint and homologous recombination processes defines a conserved oncogenic program in TNBC. This study highlights druggable molecular targets that could guide the development of pathway-directed therapies in TNBC.

Keywords triple-negative breast cancer;transcriptomics;cell cycle;DNA repair;network analysis;biomarkers.



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