Potential regulation and prognostic model of colorectal cancer with extracellular matrix genes

Abstract

Background: The tumor microenvironment (TME) of colorectal cancer (CRC) mainly comprises immune cells, stromal cells, tumor cells, as well as the extracellular matrix (ECM), which holds a pivotal position. The ECM affects cancer progression, but its regulatory roles and predictive potential in CRC are not fully understood. Methods: We analyzed transcriptomes from CRC tumors and paired normal tissues to study ECM features. Up-regulated ECM components were examined through functional enrichment analysis, and single-cell sequencing identified cell types producing collagen, regulators, and secreted factors. Transcription factor analysis and cell-cell interaction studies were conducted to identify potential regulators of ECM changes. Additionally, a prognostic model was developed using TCGA-CRC cohort data, focusing on up-regulated core ECM components. Results: Bulk RNA-seq analysis revealed a unique ECM pattern in tumors, with ECM abundance and composition significantly related to patient survival. Up-regulated ECM components were linked to various cancer-related pathways. Fibroblasts and non-fibroblasts interactions were crucial in forming the TME. Key potential regulators identified included ZNF469, PRRX2, TWIST1, and AEBP1. A prognostic model based on five ECM genes (THBS3, LAMB3, ESM1, SPRX, COL9A3) demonstrated strong associations with immune suppression and tumor angiogenesis. Conclusions: The ECM components were involved in various cell-cell interactions and correlated with tumor development and poor survival outcomes. The ECM prognostic model components could be potential targets for novel therapeutic interventions in colorectal cancer.

Keywords

• Colorectal cancer
• Extracellular matrix
• Single-cell sequencing
• Prognostic model