Nucleobindin 2 expression is an independent prognostic factor for bladder cancer

Abstract

Nucleobindin 2 (NUCB2) has been reported to play an important role in both tumorigenesis and cancer progression. This study aimed to examine the clinical significance of NUCB2 expression urothelial carcinoma of the bladder (UCB). The expression level of NUCB2 and its correlation with clinicopathological parameters was analyzed in 225 UCB tissues by immunohistochemistry. Kaplan–Meier analysis and Cox proportional hazards regression models were used to investigate the correlation between NUCB2 expression and the prognosis of UCB patients. High NUCB2 expression of UCB patients significantly correlated with aggressive clinicopathological features. Patients with high NUCB2 had shorter overall survival and recurrence-free survival in Kaplan–Meier survival curve (P = .018 and P = .001, respectively). Our results show that high expression of NUCB2 associated with aggressive clinicopathological feature and predicted unfavorable prognosis in patients with UCB might serve as feasible biomarker for clinical outcome of UCB patients after surgery and potential therapeutic target in the future.

Nucleobindin-2/Nesfatin-1—A New Cancer Related Molecule?

“…The first study on nucleobidin-2/nesfatin-1 function in cancer was made in 2012 in breast cancer patients [ 41 ]. Since then, there have been single reports on NUCB2/NESF-1 in the most common human cancers, i.e., breast, colon, gastric, bladder, ovarian, endometrial, prostate, papillary thyroid cancers, renal cell carcinoma, and glioblastoma ( Table 1 ) [ 41 , 46 , 47 , 48 , 53 ]. In general, the expression of NUCB2/NESF-1 is associated with cancer progression.…”

“…In general, the expression of NUCB2/NESF-1 is associated with cancer progression. It was a poor prognostic factor in breast cancer, clear cell renal carcinoma, gastric, prostate, endometrial, and bladder cancer [ 42 , 47 , 50 , 52 ]. In vitro studies revealed that NUCB2/NESF-1 increases invasion, migration, and proliferation in the colon, bladder, papillary thyroid, endometrial, renal, breast cancer cells, and glioblastoma [ 41 , 46 , 50 , 58 ].…”

“…Additionally, Man Cho et al presented that high expression of NUCB2/NESF-1 appeared relevant to aggressive clinicopathological features such as tumor grade, TNM stage, tumor size, and tumor number. According to results obtained from multivariate analysis, it was concluded that NUCB2/NESF-1 was the overall survival (OS) independent prognostic factor of bladder cancer [ 47 ]. No association was found between NUCB2/NESF-1 and gender or age.…”

“…As a result, there is a need to identify new proliferation-related molecules in cancers. In vitro studies showed that NUCB2/NESF-1 knockdown with siRNA or shRNA in breast cancer (MCF-7, SKBR-3), bladder cancer (T24, 5637), glioblastoma (U251, U87), endometrial cancer (Ishikawa and Sawano), and thyroid cancer (TPC-I, KI) cell lines resulted in the inhibition of cell proliferation [ 41 , 47 , 50 , 53 , 58 ]. Moreover, proliferation-related proteins (Ki-67 and PCNA) were decreased in NUCB2/NESF-1 shRNA-transfected thyroid cancer cells compared to the control.…”

Expression of NUCB2/NESF-1 in Breast Cancer Cells

“…Generally, a high expression of nucleobindin-2/NESF-1 is associated with poor outcomes in breast, colon, bladder, prostate, gastric, renal, and endometrial cancer [ 16 , 17 , 18 , 19 , 20 ]. It was demonstrated that NUCB2/NESF1 intensified proliferation, invasion, and migration processes in colon, breast, endometrial, papillary thyroid, bladder, and renal cancer cells [ 19 , 21 , 22 , 23 , 24 , 25 ].…”