Upper urinary tract urothelial carcinoma is a relatively uncommon disease and is diagnosed more frequently at advanced stages. The prognosis of these patients mainly has been related to tumor stage and grade. As a result, the definition of prognostic indicators enabling precise patient selection is mandatory for neoadjuvant or adjuvant therapies. The epithelial membrane protein (EMP2) was identified as one of the up-regulated genes by isoflavones. EMP2 overexpression suppressed foci formation, anchorage-independent growth in vitro, and tumorigenicity in severe combined immunodeficiency mice (all P < 0.05). In addition, a cross-talk between EMP2 and integrins alpha V and beta 3 was shown in the regulation of cell adhesion and migration. Higher EMP2 expression was associated with a better progression-free survival (P = 0.008) and cancer-related death (P < 0.001). EMP2 was identified as a tumor-suppressor gene in urinary tract urothelial carcinoma and may be an innovative co-targeting candidate for designing integrin-based cancer therapy.
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