Network-Based Integrative Analysis to Identify Key Genes and Corresponding Reporter Biomolecules for Triple-Negative Breast Cancer

Abstract

Background

The malignant neoplasm of the TNBC is the leading cause of death among Indian women. Recent studies identified the global burden of TNBC affecting approximately more than 40 percent of all BC cases in women worldwide. The absence of expression of receptors such as ER, PR, and HER2 characterizes TNBC.

Objectives

Due to the lack of specific targets, standard treatment options for TNBC are limited. This integrative study aims to identify key genes and provide insights into the underlying molecular mechanisms of TNBC, which can potentially lead to the development of more effective therapeutic strategies.

Material and Methodology

This study integrates PPI and WGCNA analysis of TNBC-related datasets (GSE52194 and GSE58135) to identify key genes. Subsequently, downstream analysis is conducted to explore potential therapeutic targets for TNBC.

Results

The present study renders the potential 13 key genes (PLCG2, CXCL10, CDK1, STAT1, IL6, PLK1, CCNB1, AURKA, NDC80, EGFR, 1L1B, FN1, BUB1B), along with their associated 6 TFs and 20 miRNAs, as reporter biomolecules around which the most significant changes occur. There were some miRNAs hsa-mir-449b-5p, hsa-let-7b-5p, hsa-mir-26a-5p, hsa-mir-155-5p, hsa-mir-24-3p, hsa-mir-212-3p, hsa-mir-21-5p, hsa-mir-210-3p and hsa-mir-20a-5p whose association with other cancers and other BC subtypes have been reported but their association with TNBC need to be explored. Further, enrichment and cumulative survival analysis support the disease association of identified key genes with TNBC.

Conclusion

This integrative analysis could be regarded for experimental inspection as it provides the platform for future researchers in drug designing and biomarker discovery for TNBC diagnosis and treatment.