Potential regulation and prognostic model of colorectal cancer with extracellular matrix genes
Xiaobao Yang,
Jiale Gao,
Tianzhen Zhang,
Lu Yang,
Chao Jing,
Zhongtao Zhang,
Dan Tian
Affiliations
Xiaobao Yang
Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China; State Key Lab of Digestive Health, Beijing Friendship Hospital, Capital Medical University, Beijing, China; National Clinical Research Center for Digestive Diseases, Beijing, China
Jiale Gao
Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China; State Key Lab of Digestive Health, Beijing Friendship Hospital, Capital Medical University, Beijing, China; National Clinical Research Center for Digestive Diseases, Beijing, China
Tianzhen Zhang
Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China; State Key Lab of Digestive Health, Beijing Friendship Hospital, Capital Medical University, Beijing, China; National Clinical Research Center for Digestive Diseases, Beijing, China
Lu Yang
Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China; State Key Lab of Digestive Health, Beijing Friendship Hospital, Capital Medical University, Beijing, China; National Clinical Research Center for Digestive Diseases, Beijing, China
Chao Jing
Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China; State Key Lab of Digestive Health, Beijing Friendship Hospital, Capital Medical University, Beijing, China; National Clinical Research Center for Digestive Diseases, Beijing, China
Zhongtao Zhang
Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China; State Key Lab of Digestive Health, Beijing Friendship Hospital, Capital Medical University, Beijing, China; National Clinical Research Center for Digestive Diseases, Beijing, China; Corresponding author. Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, 95Yong'an Road, Xicheng District, Beijing, 100050, China.
Dan Tian
Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China; State Key Lab of Digestive Health, Beijing Friendship Hospital, Capital Medical University, Beijing, China; National Clinical Research Center for Digestive Diseases, Beijing, China; Immunology Research Center for Oral and Systemic Health, Beijing Friendship Hospital, Capital Medical University, Beijing, China; Corresponding author. Department of General Surgery, Beijing Friendship Hospital, Capital Medical University 95 Yong'an Road, Xicheng District, Beijing, 100050, China.
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.
