development and validation of a manganese-metabolism and immune-integrated gene signature for prognosis and immune contexture in patients with colorectal cancer

Colorectal cancer (crc) is the third most frequently diagnosed cancer and the second leading cause of cancer-related mortality globally. emerging evidence identifies manganese as an important trigger for the cyclic gmp-amp synthase (cgas)-stimulator of interferon genes (sting) pathway, but prognostic signatures integrating manganese metabolism and immune pathways remain unexplored in crc.through analysis of transcriptomic and clinical data from tcga-crc and gse17538 cohorts, we established and validated an eleven-gene manganese metabolism and immune-related signature that robustly stratified crc patients into distinct risk groups with significant survival differences.high-risk patients exhibited suppressed immune microenvironments with enriched m2 macrophages and tregs and activation of oncogenic pathways. quantitative real-time polymerase chain reaction (qrt-pcr) validation confirmed dysregulation of eight signature genes in clinical crc samples, indicating the model's potential for prognostic prediction and immunotherapeutic stratification.we established a novel mirgs signature that accurately predicts crc clinical outcome. integration of manganese-based agents with immune checkpoint inhibitors (icis) represents a potential therapeutic strategy for immunotherapy-resistant crc.