High NUCB2 expression level represents an independent negative prognostic factor in Chinese cohorts of non-metastatic clear cell renal cell carcinoma patients

Abstract

BackgroundThis study aimed to investigate the prognostic significance of NUCB2 in clear cell renal cell carcinoma.Patients and MethodsThe study retrospectively enrolled a training set (182 patients) and a validation set (434 patients) with non-metastasis (pT1-3N0M0) ccRCC from two institutional medical centers of China. NUCB2 protein expression was evaluated by immunohistochemical staining of NUCB2 antibody, and its association with clinicopathological characteristics and clinical outcomes were evaluated. The NUCB2 mRNA transcription level was evaluated through TCGA KIRC cohort (190 patients). Prognostic accuracies were evaluated by C index and Akaike information criterion.ResultsIn ccRCC tissues, NUCB2 protein expression level was positively correlated with Fuhrman grade (P = 0.002 and P < 0.001, respectively). Patients with high NUCB2 mRNA transcription level (P = 0.005) and protein expression level (P = 0.024 and P < 0.001, respectively) had shorter cancer-specific survival in Kaplan-Meier survival curve. Moreover, multivariate analysis identified NUCB2 expression level as an independent prognostic factor for cancer-specific survival. Subgroup analysis suggested that NUCB2 expression significantly stratified pT1 stage patients (P < 0.001) rather than higher pT stage patients. Therefore, a new NNF prognosis model was developed to predict the cancer-specific survival in patients with pT1N0M0 stage (C-index = 0.743).ConclusionNUCB2 expression level is a powerful independent prognostic factor for CSS in patients with non-metastasis (pT1-3N0M0) ccRCC.

Nesfatin-1/Nucleobindin-2 Is a Potent Prognostic Marker and Enhances Cell Proliferation, Migration, and Invasion in Bladder Cancer

“…In order to further study functions of NUCB2 in bladder cancer, T24 and 5637 cells which are derived from human bladder cancer were transfected with special shRNA of NUCB2 to observe phenotypes. The transwell assay, MTT assay, and expression level of MMP2 and MMP9 revealed that knockdown of NUCB2 with special shRNA inhibits invasion and proliferation in bladder cancer cells which were similar to other reports in breast [ 20 ], colon [ 25 ], and prostate [ 23 ] cancer and in clear cell renal cell (ccRCC) carcinoma [ 21 ]. The wound healing assay showed that NUCB2 effected migration.…”

“…NUCB2 is widely expressed in the body and participates in several pathophysiological processes, such as appetite and body weight regulation [ 21 , 31 , 32 ] and emotion and stress regulation [ 23 ]. In recent years, NUCB2 was found to play an important role in several carcinomas.…”

“…For studies on NUCB2 in cancers, Fu et al analyzed a Chinese cohort (training set: 182 patients and validation set: 434 patients) with ccRCC patients and observed through multivariate Cox proportional hazard models that high expression level of NUCB2 was an independent poor prognostic factor for OS and CSS (cancer-specific survival). In ccRCC patients, protein expression level of NUCB2 was associated with the Fuhrman grade [ 21 ]. Similarly, Zhang et al analyzed a cohort containing188 patients with ccRCC and reported that the high expression of NUCB2 had a significant correlation with the PT stage and metastasis [ 33 ].…”

“…In breast cancer, NUCB2 is a critical prognostic factor [ 20 ]. High expression level of NUCB2 represents an independent negative prognostic factor in clear cell renal cell carcinoma (ccRCC) [ 21 ]. In prostate cancer [ 22 , 23 ], gastric cancer [ 24 ], colon cancer [ 25 ], breast carcinoma [ 19 , 20 ], and endometrial carcinoma [ 26 ], high expression of NUCB2 was linked to poor prognosis due to the enhancement in cell proliferation and migration.…”

Nucleobindin‑2 enhances the epithelial‑mesenchymal transition in renal cell carcinoma

“…In a study by Qi et al (23), NUCB-2 was highly expressed in RCC. A retrospective clinical study by Fu et al (44) found that high NUCB-2 expression levels were positively correlated with Fuhrman grade. Together, these studies have concluded that NUCB-2 is associated with poor tumor prognosis.…”