SMAD4 and colorectal carcinoma: Studies have shown that SMAD2, another member of the SMAD family, has a high correlation coefficient, suggesting a synergistic effect in tumor suppression.7,8 However, most CRC patients have mutations or decreased expression of the SMAD4 gene occur, which leads to impairment of the TGF-β signaling pathway, thereby promoting tumor proliferation and increased invasiveness.