Moreover, we established a scoring scheme capable of individually quantifying histone modification status and predicting the clinical outcomes and fluorouracil (the basic drug of adjuvant chemotherapy for colon cancer) responses, designated as “HM_score.” Moreover, by performing a genome-wide screening of the “Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)” library, we demonstrated that ZEB2 acts as a driver gene mediating the fluorouracil resistance related to histone modifier expression patterns. This evidence concerns the gene ZEB2 and malignant colon neoplasm.