RSPO4 and cancer: Fig 6A shows 10 highly reliable (RI > 90, Fig 3A) interactions predicted by NECARE between WNT3 (from the Wnt signaling pathway) and SHC2 (from the Ras signaling pathway) with the following genes: RSPO4, CDK19, NR4A1, CDK8, AREG, LHX1, VGFR3, MAPK3, ZN619 and FGF9. WNT3 is a member of the Wnt family and may play a key role in cancer through activation of the Wnt-beta-catenin-TCF signaling pathway [36]. SHC2 was located very upstream of the Ras signaling pathway and could be activated by many receptor tyrosine kinases (RTKs) in the Ras signaling pathway [6] (Fig 6A).