mA Regulator-Based Exosomal Gene Methylation Modification Patterns Identify Distinct Microenvironment Characterization and Predict Immunotherapeutic Responses in Colon Cancer.

Recent studies have highlighted the biological significance of exosomes and mA modifications in immunity. Nonetheless, it remains unclear whether the mA modification gene in exosomes of body fluid has potential roles in the tumor microenvironment (TME). Herein, we identified three different mA-related exosomal gene modification patterns based on 59 mA-related exosomal genes, which instructed distinguishing characteristics of TME in colon cancer (CC). We demonstrated that these patterns could predict the stage of tumor inflammation, subtypes, genetic variation, and patient prognosis. Furthermore, we developed a scoring mode-mA-related exosomal gene score (MREGS)-by detecting the level of mA modification in exosomes to classify immune phenotypes. Low MREGS, characterized by prominent survival and immune activation, was linked to a better response to anti-PDL1 immunotherapy. In contrast, the higher MREGS group displayed remarkable stromal activation, high activity of innate immunocytes, and a lower survival rate. Hence, this work provides a novel approach for evaluating TME cell infiltration in colon cancer and guiding more effective immunotherapy strategies.