MYCBP2 Expression Correlates With Poor Prognosis in Upper Tract Urothelial Carcinoma Patients.

Abstract

The incidence of upper tract urothelial carcinoma (UTUC) in Taiwan is high, characterized by aggressive clinical behavior and a tendency to be more invasive at diagnosis. Identifying tumorigenic genes remains an important challenge. Myc binding protein 2 (MYCBP2) regulates the cAMP, p38MAPK, TSC/mTOR, and autophagy signaling pathways in mammalian cells. MYCBP2 dysfunction has been associated with poor prognosis in leukemia, melanoma, colon, and prostate cancer. Its role in UTUC needs to be clarified. We investigated the expression of MYCBP2 in UTUC and its relationship to patient outcomes. MYCBP2 expression levels were assessed by immunohistochemistry in 110 tissue samples from UTUC patients. Higher MYCBP2 protein expression was significantly correlated with worse disease-free survival (p = 0.001) and cancer-specific survival (p = 0.007). The major clinicopathological characteristics associated with MYCBP2 expression were stage, lymphovascular invasion, distant metastasis, recurrence, and cancer death. Based on multivariate analysis, pathological stage (HR:2.31, p = 0.017) and MYCBP2 expression (HR:2.75, p = 0.015) were significant predictors of disease-free survival in UTUC. MYCBP2 is elevated in UTUC cell lines compared with immortalized uroepithelial cells. Knocking down MYCBP2 significantly suppressed cellular migration and invasion activity in BFTC909 cells. In conclusion, MYCBP2 expression might predict poor survival among UTUC patients.