Oncotarget

Research Papers:

Low neighbor of Brca1 gene expression predicts poor clinical outcome and resistance of sunitinib in clear cell renal cell carcinoma

Wen Xiao, Zhiyong Xiong, Changfei Yuan, Lin Bao, Di Liu, Xiong Yang, Wencheng Li, Junwei Tong, Yan Qu, Lei Liu, Haibing Xiao, Hongmei Yang, Xiaoping Zhang _ and Ke Chen

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Oncotarget. 2017; 8:94819-94833. https://doi.org/10.18632/oncotarget.21999

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Abstract

Wen Xiao1,*, Zhiyong Xiong1,*, Changfei Yuan1, Lin Bao1, Di Liu1, Xiong Yang1, Wencheng Li1, Junwei Tong1, Yan Qu2, Lei Liu1, Haibing Xiao1, Hongmei Yang2, Xiaoping Zhang1 and Ke Chen1

1Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China

2Department of Pathogenic Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan 430030, China

*These authors have contributed equally to this work

Correspondence to:

Xiaoping Zhang, email: xzhang@hust.edu.cn

Ke Chen, email: shenke@hust.edu.cn

Keywords: NBR1; clear cell renal cell carcinoma; prognostic markers; chemoresistance

Received: July 31, 2017     Accepted: August 28, 2017     Published: October 23, 2017

ABSTRACT

Objective: To study the expression of Neighbor of Brca1 gene (NBR1) in clear cell renal cell carcinoma (ccRCC), renal cancer cells and the chemoresistance cells and to elucidate its clinical prognostic and chemoresistance value.

Materials and Methods: We screened the NBR1 mRNA in ccRCC from The Cancer Genome Atlas (TCGA) database and examined expression levels of NBR1 mRNA in 48 cases of ccRCC tissues, renal cancer cell lines and chemoresistance cells by qRT-PCR. Then, we extended two additional data sets in oncomine datebase (https://www.oncomine.org) to further confirm the results of the TCGA database. Immunohistochemistry (IHC) assay data performed in ccRCC tissues and normal tissues were downloaded from The Human Protein Atlas.

Results: The mRNA levels of NBR1 were downregulated in TCGA-KIRC database (n = 533) and ccRCC patient samples (n=48) as well as in RCC cell lines and their chemoresistance cells. Similarly, the protein levels of NBR1 were lower in ccRCC patient samples. NBR1 level was associated with the clinical pathological stage and could discriminate metastasis, recurrence and prognosis in ccRCC patients. Low level of NBR1 mRNA showed a significance poor prognostic of overall survival (OS), disease–free survival (DFS) with univariate and multivariate analyses in ccRCC patients and sunitinib resistance.

Conclusions: Taken together, our results suggest that low level of NBR1 can predict poor clinical outcome and resistance of sunitinib in patients with ccRCC.


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