SMAD4 and colorectal carcinoma: Two-way ANOVA revealed that the induction of early-stage CRC significantly affected the downregulation of the Apc gene (Figure 5G), which is a critical regulator in the WNT signaling pathway and a known tumor suppressor gene, as well as the Smad4 gene (Figure 5H), also a suppressor gene (ANOVA, p < 0.05).