Specific expression profile of genes associated with extracellular matrix and phenotypic plasticity in triple-negative breast cancer

The tumor extracellular matrix (ECM) promotes the phenotypic plasticity of tumor cells, a key mechanism of metastasis and therapeutic resistance. Therefore, ECM is considered a promising therapeutic target for various cancer subtypes.

The aim of the study was to determine the expression profile of genes associated with ECM and phenotypic plasticity specific to triple-negative breast cancer (TNBC), and to evaluate its prognostic relevance.

To identify differentially expressed genes (DEG), we analyzed datasets (GSE65194, GSE45827) from the NCBI GEO. Both datasets have identical composition: 155 samples in total, of which 41 are TNBC samples and 11 are samples of normal breast tissue. The list of genes of interest was compiled based on data from MatrisomeDB and MSigDB. DEG analysis (|log2FC|>1, p>0.05) was performed using a software tool, which was developed using Python (pandas, numpy, matpolib) and R. The prognostic significance (HR≠1, p>0.05) was assessed by overall survival (OS) in basal-like cohorts using the KM-Plotter, comparing the first and fourth quartiles.

The analysis covered 1,027 genes. 31 genes with differential expression specific for TNBC compared to normal tissue and other BC subtypes were identified (14 elevated, 17 decreased). A significant relationship was found between the level of gene expression and OS for genes: CLEC4A, CLEC7A, IFNG, COL22A1, CRLF3, HPSE, CXCL12, OMD, and HTRA1. High expression of upregulated genes and low expression of downregulated genes were both associated with improved survival. Except for CXCL12 and OMD, which were downregulated, their high expression was associated with improved survival.

Our findings indicate that TNBC exhibits a specific expression profile of genes associated with ECM and phenotypic plasticity. We assume that some of these genes may be promising candidates for therapeutic targeting, as has also been reported by other researchers.

The study was supported by the Ministry of Science and Higher Education of the Russian Federation (project No. FSWR-2026-0015).