Molecular characteristics, clinical significance, and immune landscape of extracellular matrix remodeling-associated genes in colorectal cancer.

Abstract

Extracellular matrix (ECM) remodeling is one of the hallmark events in cancer and has been shown to be closely related to tumor immunity. Immunotherapy has evolved as an important tool to treat various cancers and improve patient prognosis. The positive response to immunotherapy relies on the unique interaction between cancer and the tumor microenvironment (TME). However, the relationship between ECM remodeling and clinical outcomes, immune cell infiltration, and immunotherapy in colorectal cancer (CRC) remains unknown. We systematically evaluated 69 ECM remodeling-associated genes (EAGs) and comprehensively identified interactions between ECM remodeling and prognosis and the immune microenvironment in CRC patients. The EAG_score was used to quantify the subtype of ECM remodeling in patients. We then assessed their value in predicting prognosis and responding to treatment in CRC. After elaborating the molecular characteristics of ECM remodeling-related genes in CRC patients, a model consisting of two ECM remodeling-related genes (MEIS2, SLC2A3) was developed for predicting the prognosis of CRC patients, Receiver Operating Characteristic (ROC) and Kaplan-Meier (K-M) analysis verified its reliable predictive ability. Furthermore, we created a highly reliable nomogram to enhance the clinical feasibility of the EAG_score. Significantly differences in TME and immune function, such as macrophages and CD8+ T cells, were observed between high- and low-risk CRC patients. In addition, drug sensitivity is also strongly related to EAG_score. Overall, we developed a prognostic model associated with ECM remodeling, provided meaningful clinical implications for immunotherapy, and facilitated individualized treatment for CRC patients. Further studies are needed to reveal the underlying mechanisms of ECM remodeling in CRC.