In addition, a novel Rspo1-Wnt-Vegfc-Vegfr3 signaling pathway has been defined to play an essential role in developmental angiogenesis [29], and an aberrant expression of VEGFC was recently found to be associated with lymph node metastasis in intrahepatic cholangiocarcinoma (IHCC) [30]. Here, RSPO1 is linked to intrahepatic cholangiocarcinoma.