Abstract
Colorectal cancer (CRC) ranks among the most prevalent malignancies globally and is the third leading cause of cancer - related deaths. Despite advancements in diagnosis and treatment, prognosis for CRC patients, especially those with advanced or metastatic disease, remains difficult due to its heterogeneity. Mitochondria, central to cellular activity, and the mitochondrial unfolded protein response (UPR(mt)), a stress - responsive pathway, are involved in various physiological and pathological processes. Recent studies have emphasized the importance of UPR(mt) in cancer biology. In this research, we explored the role of UPR - related genes (MRGs) in CRC. Through analyzing transcriptional profiles and clinical data of CRC patients, we identified different molecular subtypes according to MRG expression, which were related to patient prognosis, immune cell infiltration, and drug sensitivity. We also developed a prognostic signature based on key MRGs with strong predictive power for patient survival and treatment response. Additionally, the study of the spatial distribution of MRGs in tumor tissues revealed their heterogeneous expression and potential influence on tumor biology. Overall, our findings clarify the role of UPR in CRC and highlight its potential as a target for personalized cancer therapy.