ALDH2, CCNE1 and SMAD3 are significantly deregulated in UTUC and associated with cancer-relevant functions. A, qPCR results of ALDH2, CCNE1 and SMAD3 in 10 patients in the discovery screen plus 12 independent cases. -∆CT value normalized with U6 is presented as mean ± S.D. to show the gene expression level in tumor and normal adjacent tissues. ***P <0.001, **P <0.01, *P <0.05, paired t-test. B, Network of related genes of ALDH2, CCNE1 and SMAD3. Genes associated with ALDH2, CCNE1 and SMAD3 in terms of co-expression (blue lines), pathway relationship (red), physical interaction (green), or sharing protein domain (purple) are identified using GeneMANIA. The thickness of the line reflects the degree of association between two genes. The node size reflects how often paths start at the given gene node end up in one of the query genes and how long and heavily weighted those paths are. And the node colors indicate down-regulation (green) or up-regulation (red) of the genes. C, Representative IHC staining patterns for ALDH2, CCNE1 and SMAD3 in patients with UTUC and healthy people are shown (magnification 400X). CCNE1 and SMAD3 were strongly stained in the cancer tissues but low in the normal tissues, whereas the ALDH2 was stained low in cancer tissues.