The study looks at a protein called CTHRC1 that, when modified by a fatty acid (palmitoylation), helps breast cancer cells grow and makes the tumor environment more uneven. Researchers used big data and machine learning to show CTHRC1 is a key marker for breast cancer and that lowering its levels slows cancer cell growth. The work is focused on cancer diagnostics and therapy, not on any health‑boosting peptide for everyday use.

This study systematically screened palmitoylation-related key biomarkers in breast cancer and constructed a high-precision diagnostic model combining multi-omics data and machine learning algorithms. Following batch effect correction across datasets via the ComBat algorithm, 1,782 differentially expressed genes (DEGs) were identified and showed significant enrichment during the extracellular matrix remodeling process and in the PI3K-Akt signaling pathway, highlighting their potential roles in the regulation of cellular microenvironment and the activation of signaling network. A total of 5 core genes (<i>HBB</i>,<i> BGN</i>,<i> CTHRC1</i>,<i> FABP4</i>,<i> CD34</i>) were screened using three machine learning methods. Further analysis of gene contribution revealed that <i>CTHRC1</i> served as the key gene to affect the prediction of the model. SHAP interpretability analysis highlighted <i>CTHRC1</i> as a primary contributor to prediction models. Spatial transcriptomic mapping revealed that focal high expression of <i>CTHRC1</i> in tumor tissues was correlated with enhanced microenvironmental heterogeneity. Functional assays demonstrated that <i>CTHRC1</i> knockdown can significantly attenuate cell proliferation and clonogenic potential of breast cancer. These findings collectively elucidate that palmitoylated <i>CTHRC1</i> drives breast cancer progression by enhancing tumor cell proliferation and microenvironment heterogeneity. Clinically, <i>CTHRC1</i> has shown potential as a diagnostic biomarker and therapeutic target&#x2014;laying the foundation for the development of liquid biopsies and therapeutic targets based on <i>CTHRC1</i> to improve the precision management of breast cancer. The online version contains supplementary material available at 10.1186/s12885-025-15190-w.