SMAD4 and colorectal adenocarcinoma: For instance, there were findings suggest that the loss of Smad4 and PTEN may lead to more aggressive disease and poor prognosis in patients with colorectal adenocarcinoma compared to the loss of SMAD4 or PTEN alone [28], pancreatic cancer [29], lung cancer [30], and invasive intestinal-type gastric cancer [22].