These findings support the idea that enhanced p53-CDKN1A signaling in MSI tumors may reduce 5-FU sensitivity, whereas MSS tumors with lower CDKN1A expression may be more susceptible to 5-FU-induced cytotoxicity, consistent with prior evidence linking altered p53 pathway activity to chemoresistance in MSI CRC [85]. This evidence concerns the gene TP53 and colorectal carcinoma.