Such reactivation of HH signaling pathway leads to regulation downstream gene transcription of Cyclin D1, PAX2, VEGF, and TGF-β.248 The mRNA levels of Shh, Smo and Gli1 were higher in CRCC tissue compared with control kidney tissue in different degrees.249 Gli3, Ptch1, Dhh, and Shh were highly expressed in in higher grade tumor as Dhh expression can be recognized as an independent predictor of CRCC survival.250 Multiple studies show antitumor potential in human RCC by targeting HH signaling pathway.251,252. This evidence concerns the gene PTCH1 and neoplasm.