# Single-cell and transcriptome analyses revealed CTHRC1 a potential therapeutic target mediating invasion and tumor microenvironment in TNBC: experimental validation

## TL;DR

This study identifies CTHRC1 as a key molecule in triple-negative breast cancer that influences tumor invasion and the tumor microenvironment.

## Contribution

The novel contribution is the experimental validation of CTHRC1's role in modulating tumor invasion and immune cell infiltration in TNBC.

## Key findings

- CTHRC1 expression increases with tumor progression and correlates with invasive genes in TNBC.
- CTHRC1-positive cancer-associated fibroblasts modulate M2-type macrophage activity in the tumor microenvironment.
- Immunofluorescence confirms CTHRC1's role in immune cell infiltration and tumor cell invasion.

## Abstract

Investigating the pivotal role of CTHRC1 in the tumor microenvironment of triple-negative breast cancer (TNBC).

The RNA transcriptomic data obtained from the Cancer Genome Atlas and single-cell sequencing data from TNBC in Gene Expression Omnibus (GEO) were acquired and subjected to analysis. A comprehensive investigation was conducted with a specific focus on characterizing CTHRC1 in TNBC and its correlation with invasive genes. Furthermore, additional analyses were performed to explore the relationship between CTHRC1, tumor immune cell infiltration, and immunotherapy in TNBC. The expression of CTHRC1 in the tumor microenvironment, cellular differentiation, and cellular communication was systematically analyzed using single-cell data from TNBC.

The expression of CTHRC1 in patients with TNBC gradually increases concomitantly with the progression of tumor T-stage and N-stage. Simultaneously, there is a concurrent increase in the expression of most invasive gene sets. Furthermore, there is a significant augmentation in both infiltration abundance and activity of M2-type macrophages associated with elevated levels of CTHRC1 expression. Single-cell data reveal an upregulated expression of the invasive gene set in CTHRC1-positive cancer associated fibroblasts (CAFs), thereby modulating their interaction with M2-type macrophages. Multiple immunofluorescence analyses confirmed that CTHRC1 modulates immune cell infiltration and tumor cell invasion through the mediation of CAFs.

CTHRC1 was a molecule that exhibits characteristic expression in TNBC. CTHRC1 positive CAFs exert regulatory effects within the immunosuppressive microenvironment of TNBC by modulating M2-type macrophages.