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

Low neighbor of Brca1 gene expression predicts poor clinical outcome and resistance of sunitinib in clear cell renal cell carcinoma.
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Brca1 基因低邻居表达预示着透明细胞肾细胞癌中不良的临床结果和舒尼替尼的耐药性

DOI:
10.18632/oncotarget.21999
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发表时间:
2017-11-07
期刊:
影响因子:
--
通讯作者:
Chen K
Chen K
中科院分区:
其他
文献类型:
--
作者:
Xiao W;Xiong Z;Yuan C;Bao L;Liu D;Yang X;Li W;Tong J;Qu Y;Liu L;Xiao H;Yang H;Zhang X;Chen K

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目的研究肾透明细胞癌(ccRCC)、肾癌细胞及耐药细胞中Brca 1基因邻居(NBR 1)的表达,探讨其临床预后及耐药价值。我们从癌症基因组图谱(TCGA)数据库中筛选了ccRCC中的NBR 1 mRNA,并通过qRT-PCR检测了48例ccRCC组织、肾癌细胞系和化疗耐药细胞中NBR 1 mRNA的表达水平。然后,我们在oncomine数据库(https://www.example.com)中扩展了两个额外的数据集,以进一步确认TCGA数据库的结果。www.oncomine.org从The Human Protein Atlas下载在ccRCC组织和正常组织中进行的免疫组织化学(IHC)测定数据。在TCGA-KIRC数据库(n = 533)和ccRCC患者样本(n=48)以及RCC细胞系及其化学抗性细胞中,NBR 1的mRNA水平下调。类似地,在ccRCC患者样品中,NBRl的蛋白质水平较低。NBR 1水平与临床病理分期有关,可作为鉴别ccRCC患者转移、复发及预后的指标。单因素和多因素分析显示,在舒尼替尼耐药的ccRCC患者中,低水平的NBR 1 mRNA表达对总生存期(OS)和无病生存期(DFS)的预后有显著影响。总之,我们的研究结果表明,低水平的NBR 1可以预测ccRCC患者的临床结局较差和舒尼替尼耐药。
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. 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. 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. 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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