Low expression of ZSCAN4 predicts unfavorable outcome in urothelial carcinoma of upper urinary tract and urinary bladder

BackgroundWith the advance in genome-wide analyses, genetic alternations have been found to play an important role in carcinogenesis and aggressiveness of UC. Through bioinformatic analysis of gene expression profiles of urinary bladder urothelial carcinoma (UBUC) from publicly available GEO dataset (GSE31684), Zinc finger and SCAN domain containing 4 (ZSCAN4) was identified as a significant downregulated gene in muscle-invasive bladder cancer when compared with non-muscle-invasive bladder cancer.MethodsThe expression of ZSCAN4 was evaluated by immunohistochemistry in 340 upper urinary tract urothelial carcinomas (UTUCs) and 295 UBUCs. The expression profiles of ZSCAN4 and potential signaling pathways were analyzed bioinformatically.ResultsIn UTUC, low expression of ZSCAN4 was significantly associated with advanced primary pT stage (P = 0.011), increased nodal metastasis (P = 0.002) and increased vascular invasion (P = 0.019). In UBUC, low expression of ZSCAN4 was significantly correlated with advanced primary pT stage (P < 0.001), increased nodal metastasis (P = 0.001), high histological grade (P = 0.003) and increased vascular invasion (P = 0.003). In survival analysis, low expression of ZSCAN4 acted as an independent negative prognostic factor for disease-specific survival and metastasis-free survival both in UTUC and UBUC. Gene ontology analysis showed that ZSCAN4 mRNA and its co-downregulated genes are associated with the mitotic cell cycle.ConclusionsLow expression of ZSCAN4 predicted worse outcome in urothelial carcinoma and might have potential regulatory role in cell mitosis.

Automated summary

Zinc finger and SCAN domain containing 4 (ZSCAN4) is downregulated in muscle-invasive bladder cancer and its low expression is significantly correlated with tumor progression, metastasis, and vascular invasion in both upper urinary tract urothelial carcinoma (UTUC) and urinary bladder urothelial carcinoma (UBUC). Furthermore, low expression of ZSCAN4 serves as an independent negative prognostic factor for both diseases. Gene ontology analysis reveals that ZSCAN4 and its co-downregulated genes are associated with the mitotic cell cycle.