In addition, hyperinsulinemia leads to decreased hepatic synthesis of insulin-like growth factor (IGF)-binding protein 1 (IGFBP-1) and protein 2 (IGFBP-2) and may result in increased bioactivity of IGF-I (34, 35), which directly induces the development of CRC due to its mitogenic and antiapoptotic actions (33). Here, PROS2P is linked to hyperinsulinism.