The activation of Wnt signaling has been detected in cholangiocarcinoma, and the validated mutations identified so far are an inhibitory ring finger protein 43 (RNF43) mutation, overexpression of Wntless, and hypermethylation of secreted frizzled-related protein 2 (SFRP2) [176,177,178]. Here, SFRP2 is linked to cholangiocarcinoma.