High Jagged1 expression predicts poor outcome in clear cell renal cell carcinoma.

OBJECTIVE: The pathological roles of Notch pathway in renal cell carcinoma are still unclear, although Notch signaling has been shown to have an effect on many malignant tumors. In this study, Jagged1 was detected to examine its expression pattern and clinical significance in renal cell carcinoma.

METHODS: Normal and cancerous kidney tissues from three renal cell carcinoma patients were analyzed using western blot and reverse transcriptase-polymerase chain reaction for Jagged1 expression. Subsequently, extensive immunohistochemistry was performed to detect Jagged1 expression in 129 renal cell carcinoma cases. Clinicopathological data for these patients were evaluated. The prognostic significance was assessed using the Kaplan-Meier survival estimates and log-rank tests. A multivariate study with the Cox proportional hazard model was used to evaluate the prognosis-related aspects.

RESULTS: Western blot and polymerase chain reaction results showed markedly increased Jagged1 protein and mRNA levels in renal cell carcinoma tissues compared with normal kidney tissues, which was further verified by immunohistochemical analysis. The expression level of Jagged1 was strongly associated with tumor size, nuclear grade and TNM stage. In addition, high Jagged1 expression was statistically linked to reduced overall and disease-free survival, especially at the early stage (P < 0.001 and <0.001, respectively). Jagged1 expression was found to be an independent prognostic factor for both overall survival and disease-free survival in multivariate analysis (P = 0.035 and 0.028, respectively).

CONCLUSIONS: Notch signaling may play an important role in the progress of renal cell carcinoma. Jagged1 expression may be useful for predicting prognosis in patients with renal cell carcinoma, especially at the early stage.