Research Papers:

A three-molecule score based on Notch pathway predicts poor prognosis in non-metastasis clear cell renal cell carcinoma

Zheng Liu, Qiang Fu, Hangcheng Fu, Zewei Wang, Le Xu, Huimin An, Yanfeng Li _ and Jiejie Xu

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Oncotarget. 2016; 7:68559-68570. https://doi.org/10.18632/oncotarget.11849

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Zheng Liu1,*, Qiang Fu1,*, Hangcheng Fu1,*, Zewei Wang1, Le Xu2, Huimin An2, Yanfeng Li3, Jiejie Xu1

1Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China

2Department of Urology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China

3Department of Orthopaedic Surgery, Shanghai Jiaotong University Affiliated Sixth People’s Hospital, Shanghai, China

*These authors have contributed equally to this work

Correspondence to:

Yanfeng Li, email: [email protected]

Jiejie Xu, email: [email protected]

Keywords: clear cell renal cell carcinoma, Jagged1, Notch1, Hes1, prognostic factor

Received: May 08, 2016    Accepted: August 25, 2016    Published: September 06, 2016


We constructed a three-molecule score based on the expression of Notch pathway molecules: Jagged1, intracellular Notch1 (ICN1) and Hes1 (JIH score). To assess prognostic value of the JIH score in non-metastasis clear cell renal cell carcinoma (ccRCC), we identified 467 patients who underwent nephrectomy during 2008-2009 as our study population. Immunohistochemistry was used to evaluate the expression of these three molecules. Cox regression models were applied to construct the JIH score, while Kaplan-Meier methods, multivariate analyses and nomogram were used to explore prognostic value of the JIH score. Our result confirmed that JIH score was an independent prognosticator for both overall survival (OS) and recurrence-free survival (RFS). Survival analyses showed that a higher JIH score indicated worse clinical outcomes (JIH score 3: 58.3% and 58.0% for 6-year OS and RFS, respectively; JIH score 0: 96.7% and 91.6% for 6-year OS and RFS, respectively). Nomograms based on JIH score and other conventional clinicopathological features had a better capability in predicting patients with pT1 stage disease for both OS and RFS (84.6% and 83.9%, respectively). The JIH score is a novel prognosticator representing activation of Notch pathway for non-metastasis ccRCC, and raises an alternative strategy for excavating potential biomarkers for signal pathways.

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