Overall, in combination with the functional antagonism of RUNX3 activity by TLE6D observed in colon cancer cells, the correlation of RUNX3 and TLE6D expression in human CRCs suggests that TLE6D may interact with the RUNX3 GI epithelial tumor suppressor and inactivate RUNX3 in a subset of CRCs independent of MSI status. Here, RUNX3 is linked to malignant colon neoplasm.