In summary, the novel TME-related signature consisting of CADM3, LEP, CD1B, PDE1B, CCL22, ABI3BP, IGLON5, SELE, and TGFB1 is an effective, practical, and quantitative approach for clinicians to predict survival and to provide individualized treatment for colon cancer patients and is expected to be further utilized in future clinical practice. Here, IGLON5 is linked to malignant colon neoplasm.