SMAD4 and non-small cell lung carcinoma: Mutations in SMAD4, as well as the loss or reduction of its expression, have been found to be closely associated with the progression and survival of patients with non-small cell lung cancer (NSCLC).8 Furthermore, in hepatocellular carcinoma (HCC), loss of SMAD4 has been implicated as a mechanism by which HCC cells gain invasive and metastatic capabilities.