SMAD4 and colorectal carcinoma: In CRC, mutations in the SMAD4 gene are often closely associated with the aggressiveness of the disease, increased ability to metastasize, tumor location, and poor prognosis of CRC patients.2,29 Numerous studies have shown that patients with CRC lacking the SMAD4 gene tend to have a worse prognosis compared to those without this deletion, exhibiting shorter recurrence-free survival (RFS).