Epithelial Membrane Protein 2 Is a Prognostic Indictor for Patients with Urothelial Carcinoma of the Upper Urinary Tract

Abstract

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 αV and β3 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.

DDR2 overexpression in urothelial carcinoma indicates an unfavorable prognosis: a large cohort study

“…DDR2 expression level was examined on urothelial cancer cell lines including RT4, SW780 (grade 1), TSGH8301 (grade 2), UMUC3, T24, J82, TCCSUP, BFTC905, BFTC909, and HT1197 (grade 3) [15, 52]. Real time PCR reveals high DDR2 mRNA expression in two grade 3 cell lines, UMUC3 and BFTC909 (Figure 6A).…”

“…BFTC909 was derived from the rare sarcomatoid variant of UC in renal pelvis [52]. UMUC3, SW780, T24, J82, and HT1197 were purchased from American Type Culture Collection (Manassas, VA 20108, USA).…”

The cAMP responsive element binding protein 1 transactivates epithelial membrane protein 2, a potential tumor suppressor in the urinary bladder urothelial carcinoma

“…Our previous study using suppression subtractive hybridization approach identified that genistein induced epithelial membrane protein 2 ( EMP2 ) mRNA in UBUC-derived RT4 cells. High EMP2 immunointensity was recognized as a prognostic indicator for patients with upper tract urothelial carcinoma (UTUC), possibly via suppression of cell proliferation [ 12 ]. Relative to primary UBUC, UTUC is uncommon [ 13 ], with notable differences at the genetic, molecular and clinical levels [ 14 – 16 ].…”

“…In humans, EMP2 protein has a discrete cell type and tissue distribution, with high levels observed in the lung and moderate levels in the eye, heart, thyroid and intestine [ 21 , 22 ]. Results from our previous study [ 12 ], data mining and the fact that membrane proteins belong to the largest class of drug targets [ 23 ], prompted us to systematically analyze the relevance of EMP2 immunointensity and clinicopathological features in UBUC patients. Biological functions and a potential transcription factor of EMP2 were also studied using three UBUC-derived cell lines, RT4, TSGH8301 and J82.…”

Review of the GAS3 Family of Proteins and their Relevance to Cancer

“…Initially, EMP2 was also reported to have an apoptotic effect in a B-cell lymphoma cell line, and similar roles have been proposed in nasopharyngeal and urinary tract urothelial carcinoma. 61,74,75 However, multiple other studies suggest that EMP2 functions as an oncoprotein. Using microarray technology, gene profiling suggests that EMP2 mRNA is upregulated in a number of cancers including breast, ovarian, endometrial, and primary CNS malignancies.…”