However, it was demonstrated that in spheroids, all genes in Notch signaling are significantly upregulated, particularly Jagged1, DLL3 and Notch1. High Jagged1 expression has been demonstrated to predict a worse outcome in breast cancer (35,36), renal cell carcinoma (37) and colon adenocarcinoma (38). Here, DLL3 is linked to hereditary clear cell renal cell carcinoma.