Multi-omics driven immune classification of colorectal cancer: Implications for immunotherapy efficacy prediction and enhancement with WNT signaling inhibition.
Summary
This study developed a novel immune classification for colorectal cancer (CRC) through integrative multi-omics analysis. By utilizing gene expression, mutation, and methylation profiles from two large CRC cohorts, three distinct clusters (MotifCC) were identified, each with unique molecular and immune characteristics. Cluster1, featuring high WNT pathway activation, exhibited the worst prognosis and a tumor-promoting microenvironment, suggesting benefit from a combination of immunotherapy and WNT-targeted treatment. Cluster2, with low immune infiltration and high glycolysis intensity, might respond to metabolism inhibitors, while Cluster3, characterized by high gene methylation, high tumor mutation burden, and microsatellite instability, showed a better response to immunotherapy. This classification provides valuable insights for understanding CRC heterogeneity and tailoring immunotherapy strategies.
Analysis
This research is of paramount importance for translational medicine and clinical oncology practice. By proposing a multi-omics immune classification for colorectal cancer, it provides a framework for better predicting immunotherapy response and developing personalized therapeutic strategies. The identification of "cold" subtypes (Cluster1 and Cluster2) and their molecular characteristics paves the way for combination therapies, such as WNT signaling inhibition or metabolic inhibitors, to convert these tumors into "hot" tumors, thereby enhancing immunotherapy efficacy and offering new prospects for non-responding patients.