GPX2，CDCA5，HAS3與BCAT1對於泌尿上皮癌之預後影響:以轉錄體資料庫分析

Abstract

Urothelial carcinoma (UC) is the most common histopathological type of urinary tract neoplasm. In spite of the less frequent prevalence and more advanced disease at diagnosis of upper urinary tract urothelial carcinoma (UTUC) compared with urinary bladder urothelial carcinoma (UBUC), tumorigenesis of UC arising from both areas may share a similar pathway. By data mining from two published transcriptomic databases of UBUCs (GSE31684 and GSE32894), we identified four different genes as the most significant gene showing stepwise up- or down-regulation from early tumor development to progression among those associated with their gene ontology. These are glutathione peroxidase 2 (GPX2) among those response to oxidative stress (GO:0006979), cell division cycle associated 5 (CDCA5) among those associated with G1-S transition of the mitotic cell cycle (GO:0000082), hyaluronan synthase-3 (HAS3) among genes associated with hyaluronan synthase activity (GO:0050501), and branched-chain amino acid transaminase 1 (BCAT1) among those associated with amino acid biosynthetic process (GO:0008652). Quantitative real-time PCR analyses revealed that low transcript levels of GPX2, as well as high transcript level of CDCA5 and BCAT1 were significantly associated with higher pT status and/or lymph node metastasis in both UTUCs and UBUCs (all p<0.05). By immunohistochemistry, we also demonstrated GPX2 and HAS3 protein down-regulation, as well as CDCA5 and BCAT1 protein up-regulation were associated with adverse clinicopathological parameters to statistical significance in both groups (all p<0.05). Furthermore, down-regulation of GPX2 and HAS3, and up-regulation of CDCA5 and BCAT1 predicted worse disease-specific survival and metastasis-free survival at both univariate and multivariate analyses.