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

Background: This study aimed to investigate the prognostic significance of NUCB2 in clear cell renal cell carcinoma. Patients and Methods: The 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. Results: In 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). Conclusion: NUCB2 expression level is a powerful independent prognostic factor for CSS in patients with non-metastasis (pT1-3N0M0) ccRCC.