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Abstract Colon adenocarcinoma (COAD) is one of the most common types of cancer. The interconnection between non-apoptotic cell death and COAD has not been adequately addressed. In our study, an integrative bioinformatics analysis was performed to explore non-apoptotic cell death-related biomarkers in COAD. ENO2 was determined as a potent biomarker for prognosis, drug response, immunity, and immunotherapy prediction. We used EdU and RT-qPCR assays to test our hypothesis and investigate how the ENO2 gene may influence or regulate cancer-related processes. ENO2 was expected to be a potential target in COAD.