Unveiling immune-related gene signatures in triple negative breast cancer through integrated transcriptomic analysis

Priyanga Paranthaman, Department of Biotechnology, School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, India.
Ramanathan Karuppasamy, Department of Biotechnology, School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, India.
Shanthi Veerappapillai, Department of Biotechnology, School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, IndiaFollow

Abstract

Background: Triple-negative breast cancer (TNBC) is an aggressive subtype with limited treatment options and poor prognosis. Understanding the underlying molecular mechanisms, particularly immune-related gene networks, is critical for identifying novel therapeutic targets. Aim: This study aimed to identify immune-related hub genes involved in TNBC progression by integrating microarray and RNA sequencing data. Methods: We integrated microarray and RNA sequencing datasets from five Gene Expression Omnibus (GEO) studies (GSE36295, GSE37751, GSE61724, GSE38959, and GSE58135) to identify differentially expressed genes (DEGs). Protein–protein interaction (PPI) networks were constructed using the STRING database. Key modules and hub genes were identified through network analysis. Functional enrichment was performed to elucidate biological pathways, while immune infiltration analysis assessed associations with the tumor microenvironment. Drug–gene interaction databases were queried for FDA-approved compounds targeting hub genes. Results: The PPI network revealed 179 nodes and 781 edges, indicating high connectivity. Module analysis highlighted a significant cluster with the identified key genes such as CDK1, BUB1B, CCNA2, BUB1, CCNB1, KIF20A, CENPF, TOP2A, KIF11 and MELK validated at both mRNA and protein levels. Functional enrichment revealed pathways related to cell cycle control, chromosome segregation, and kinase activity. Immune infiltration analysis indicated involvement of B cells, macrophages, and neutrophils in the TNBC microenvironment. Drug–gene mapping revealed a lack of FDA-approved drugs targeting certain key hub genes. Conclusion: This integrative study identified key immune-related hub genes driving TNBC progression, with KIF20A emerging as a promising yet underexplored target. Drug repurposing strategies focusing on KIF20A and other identified hub genes may accelerate the development of effective treatments, offering valuable insights for future therapeutic and prognostic evaluations in TNBC.

Recommended Citation

Paranthaman, Priyanga; Karuppasamy, Ramanathan; and Veerappapillai, Shanthi (2026) "Unveiling immune-related gene signatures in triple negative breast cancer through integrated transcriptomic analysis," BioMedicine: Vol. 16 : Iss. 2 , Article 5.
DOI: 10.37796/2211-8039.1708

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