Delta-like ligand 4: A predictor of poor prognosis in clear cell renal cell carcinoma.
Delta-like ligand 4: A predictor of poor prognosis in clear cell renal cell carcinoma.
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DOI：
10.3892/ol.2014.2554
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发表时间：
2014-12
期刊：
影响因子：
2.9
通讯作者：
Yue Z
中科院分区：
文献类型：
--
作者：
Wang W;Yu Y;Wang Y;Li X;Bao J;Wu G;Chang H;Shi T;Yue Z
Delta 样配体 4 (Dll4)-Notch 信号传导在肿瘤血管生成中很重要；然而，D114 检测对透明细胞肾细胞癌 (CCRCC) 患者的预后价值仍不清楚。本研究旨在确定 Dll4 高表达水平的存在是否与 CCRCC 根治性切除后的不良预后相关。通过蛋白质印迹法测定四对 CCRCC 组织和邻近正常肾组织样本中 D114 的表达水平。手术标本包括 121 份 CCRCC 组织样本和 65 份正常肾组织样本，均取自 CCRCC 患者。对样本进行免疫组织化学评估，以确定 Dll4 和血管内皮生长因子受体 2 (VEGFR-2) 的表达水平。通过Kaplan-Meier法和Cox回归分析评估Dll4表达水平的预后意义。通过χ2检验和多因素Logistic回归分析Dll4表达水平与VEGFR-2表达水平、肿瘤分期、肿瘤分级和转移之间的相关性。 Western blotting结果显示，与癌旁组织相比，CCRCC组织中Dll4蛋白表达水平显着升高。从手术标本分析来看，53例（43.8%）CCRCC患者表现出免疫组织化学高Dll4表达水平，68例（56.2%）患者表现出低Dll4表达水平。生存曲线显示，Dll4高表达患者的生存时间明显短于Dll4低表达患者（P<0.001）。多变量生存分析表明，Dll4 高表达水平的存在与总生存期和无进展生存时间的缩短独立相关（P 分别为 0.021 和 0.034）。 Dll4 和 VEGFR-2 表达水平之间也存在正相关性 (P=0.001)。总之，结果表明，CCRCC患者中Dll4高表达水平的存在与VEGFR-2高表达水平、肿瘤分级、肿瘤分期和不良预后明显相关。因此，抑制 Dll4 可能对 CCRCC 抗 VEGF 疗法耐药的肿瘤发挥有效的生长抑制作用。
Delta-like ligand 4 (Dll4)-Notch signaling is important in tumor angiogenesis; however, the prognostic value of D114 detection in patients with clear cell renal cell carcinoma (CCRCC) remains unclear. The present study aimed to determine whether the presence of high Dll4 expression levels was correlated with poor prognosis in CCRCC following curative resection. The D114 expression levels in four paired samples of CCRCC tissues and adjacent normal renal tissues were assayed by western blotting. Surgical specimens comprised 121 CCRCC tissue samples and 65 normal renal tissue samples, obtained from patients with CCRCC. The specimens were immunohistochemically assessed to determine Dll4 and vascular endothelial growth factor receptor 2 (VEGFR-2) expression levels. The prognostic significance of Dll4 expression levels was evaluated by the Kaplan-Meier method and Cox regression analysis. The correlation between Dll4 expression levels and VEGFR-2 expression levels, tumor stage, tumor grade and metastasis, was examined by χ2 test and multivariate logistic regression. As determined by the western blotting results, Dll4 protein expression levels were significantly increased in CCRCC tissues compared with those in adjacent non-cancerous tissues. From the analysis of the surgical specimens, 53 (43.8%) CCRCC patients exhibited immunohistochemically high Dll4 expression levels and 68 (56.2%) patients exhibited low Dll4 expression levels. The survival curves revealed that the patients with high Dll4 expression levels had significantly shorter survival times than the patients with low Dll4 expression levels (P<0.001). Multivariate survival analysis demonstrated that the presence of high Dll4 expression levels was independently associated with reduced overall survival and progression-free survival times (P=0.021 and 0.034, respectively). A positive correlation was also identified between Dll4 and VEGFR-2 expression levels (P=0.001). In conclusion, the results show that the presence of high Dll4 expression levels was clearly associated with high VEGFR-2 expression levels, tumor grade, tumor stage and poor prognosis in CCRCC patients. Therefore, inhibition of Dll4 may exert potent growth inhibitory effects on tumors resistant to anti-VEGF therapies for CCRCC.
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影响因子：
11.5
作者：
Patel, Nilay S.;Dobbie, Michael S.;Harris, Adrian L.
通讯作者：
Harris, Adrian L.
影响因子：
11.2
作者：
Patel, NS;Li, JL;Harris, AL
通讯作者：
Harris, AL
影响因子：
23.4
作者：
Martinez-Salamanca, Juan I.;Huang, William C.;Libertino, John A.
通讯作者：
Libertino, John A.
DOI：
10.1073/pnas.0611177104
发表时间：
2007-02-27
影响因子：
11.1
作者：
Suchting, Steven;Freitas, Catarina;Eichmann, Anne
通讯作者：
Eichmann, Anne
影响因子：
6
作者：
Jubb, Adrian M.;Soilleux, Elizabeth J.;Harris, Adrian L.
通讯作者：
Harris, Adrian L.