Increased B4GALT1 expression associates with adverse outcome in patients with non-metastatic clear cell renal cell carcinoma
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Huyang Xie1,2,*, Yu Zhu1,2,*, Huimin An1,2,*, Hongkai Wang1,2, Yao Zhu1,2, Hangcheng Fu3, Zewei Wang3, Qiang Fu3, Jiejie Xu3, Dingwei Ye1,2
1Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China
2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
3Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China
*These authors have contributed equally to this work
Jiejie Xu, email: [email protected]
Dingwei Ye, email: [email protected]
Keywords: clear cell renal cell carcinoma, B4GALT1, overall survival, prognostic biomarker, nomogram
Received: December 16, 2015 Accepted: March 28, 2016 Published: April 15, 2016
B4GALT1 is one of seven beta-1, 4-galactosyltransferase (B4GALT) genes, which has distinct functions in various malignances. Here, we evaluate the association of B4GALT1 expression with oncologic outcome in patients with non-metastatic clear cell renal cell carcinoma (ccRCC). A retrospective analysis of 438 patients with non-metastatic ccRCC at two academic medical centers between 2005 and 2009 was performed. The first cohort with 207 patients was treated as training cohort and the other as validation cohort. Tissue microarrays (TMAs) were created in triplicate from formalin-fixed, paraffin embedded specimens. Immunohistochemistry (IHC) was performed and the association of B4GALT1 expression with standard pathologic features and prognosis were evaluated. B4GALT1 expression was significantly associated with tumor T stage (P<0.001 and P<0.001, respectively), Fuhrman grade (P<0.001 and P<0.001, respectively) and necrosis (P=0.021 and P=0.002, respectively) in both training and validation cohorts. And high B4GALT1 expression indicated poor overall survival (OS) (P<0.001 and P<0.001, respectively) in the two cohorts. Furthermore, B4GALT1 expression was identified as an independent adverse prognostic factor for survival (P=0.007 and P=0.002, respectively). Moreover, the accuracy of established prognostic models was improved when B4GALT1 expression was added. Therefore, a predictive nomogram was generated with identified independent prognosticators to assess patients’ OS at 5 and 10 years. Increased B4GALT1 expression is a potential independent adverse prognostic factor for OS in patients with non-metastatic ccRCC.
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