Studies have shown that the absence or reduced expression of SMAD4 is often associated with higher tumor stages, increased aggressiveness, and metastatic potential.2,61–63 Moreover, patients with reduced expression of SMAD4 tend to have shorter disease-free survival (DFS) and overall survival (OS), making SMAD4 an effective independent prognostic factor for predicting patient survival probabilities and risk of disease progression.64 This evidence concerns the gene SMAD4 and neoplasm.