COMP promotes the progression of colorectal cancer by regulating epithelial mesenchymal transition

Background: Epithelial-mesenchymal transition (EMT) plays a crucial role in the progression and metastasis of colorectal Cancer (CRC). This study investigates the molecular mechanisms of EMT and its prognostic biomarkers in CRC.

Methods: Multi-omics bioinformatics analyses were conducted using CRC transcriptomic datasets from GEO and TCGA. EMT-related differentially expressed genes (EMT-DEGs) were identified and subjected to pathway enrichment and machine learning-based prognostic modeling. COMP was selected as a hub gene for further validation. Single-cell RNA Sequencing (scRNA-seq) data were also analyzed to determine the cell-type-specific expression pattern of COMP and EMT-DEGs. Clinical CRC tissue samples were analyzed via RT-qPCR, Western blot, and histology. Functional assays in HT-29 cells assessed the effects of COMP knockdown on EMT markers, proliferation, Apoptosis, invasion, and migration.

Results: EMT was significantly enriched in CRC, with 36 EMT-DEGs identified. These DEGs were enriched in pathways such as ECM-receptor interaction, focal adhesion, and the PI3K-Akt signaling pathway. Among the constructed machine learning models, the random survival forest (RSF) model demonstrated the strongest ability to predict CRC prognosis. This model stratified CRC patients into high-risk and low-risk groups, with poorer prognosis observed in the high-risk group. COX regression forest plots and Kaplan-Meier survival analysis identified COMP as a top EMT-related prognostic gene enriched in pathways including ECM-receptor interaction and PI3K-Akt signaling. High COMP expression correlated with poor patient prognosis and EMT marker dysregulation in metastatic CRC tissues. In vitro, COMP knockdown significantly reduced mesenchymal markers, restored E-cadherin, and inhibited proliferation and invasion of CRC cells.

Conclusion: EMT plays a vital role in CRC progression and metastasis, with COMP identified as a key prognostic biomarker and potential therapeutic target. This study provides new insights into the molecular mechanisms and intervention strategies for CRC metastasis.

Supplementary Information: The online version contains supplementary material available at 10.1186/s12885-025-15000-3.

COMP; Colorectal cancer; Epithelial-mesenchymal transition; Metastasis.