Uncovering Novel
Gene Signatures involved in chromosomes segregation in Triple-Negative Breast Cancer
using Differential Transcriptome Analysis
Tiwari Prashant Kumar, Mishra Santosh Kumar, Singh Himanshu Narayan and Kumar Sanjay
Res. J. Biotech.; Vol. 20(11); 85-97;
doi: https://doi.org/10.25303/2011rjbt085097; (2025)
Abstract
Triple-negative breast cancer (TNBC), a heterogeneous subtype of breast cancer (BC)
is characterized by the absence of estrogen (ER), progesterone (PR) and HER2 receptors.
TNBC and non-TNBC exhibit distinct biological behaviours, primarily due to differentially
expressed genes (DEGs). This study is focusing to identify key DEGs that may have
association with TNBC pathogenesis. mRNA datasets (GSE36295, GSE45255 and GSE163882)
comprise of 116 TNBC and 295 non-TNBC patients and were analyzed using the “affy”
R-package for expression profiling. Pathway enrichment analysis identified biological
processes associated to cancer progression. Of the 998 DEGs, 169 genes were upregulated
and 829 genes were downregulated with significant changes (p< 0.001).
Notably, several genes were identified that are linked with highly activated cancer
progression pathways, among them MYBL2, KIF23, BRIP1, CENPN, KIFC1, XRCC3 and CDCA8
are associated with chromosomal segregation pathways. For the identification of
regulating miRNAs, Enrichr web tool was used demonstrating that MYBL2, BRIP1 and
CENPN genes are regulated by miR-4454, miR-4632 and miR-1307. Furthermore, the sensitivity
and specificity of these genes were assessed utilizing receiver operating characteristic
(ROC), that exhibited KIF23 and BRIP1 having highest AUC (Area Under Curve) value
of 0.79 and 0.77 respectively. That suggested their strong potential as a biomarker
for diagnosis of TNBC.
