High expression of HuR in cytoplasm, but not nuclei, is associated with malignant aggressiveness and prognosis in bladder cancer.
High expression of HuR in cytoplasm, but not nuclei, is associated with malignant aggressiveness and prognosis in bladder cancer.
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DOI：
10.1371/journal.pone.0059095
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Sakai H
中科院分区：
文献类型：
--
作者：
Miyata Y;Watanabe S;Sagara Y;Mitsunari K;Matsuo T;Ohba K;Sakai H
人抗原R（HuR）调节mRNA的稳定性，并与细胞增殖、血管生成和淋巴管生成相关。然而，HuR在膀胱癌中的临床意义和病理作用尚不清楚。本研究的主要目的是阐明HuR表达及其临床意义与癌细胞增殖、血管生成、淋巴管生成以及环氧合酶（考克斯）-2和血管内皮生长因子（VEGF）-A、-C和-D表达的关系。应用免疫组化方法检测122例膀胱癌组织中上述蛋白的表达。分别用细胞质和细胞核染色评价HuR表达。细胞增殖、血管生成和淋巴管生成以Ki-67阳性细胞（增殖指数，PI）、CD 34染色血管（微血管密度，MVD）和D2-40染色血管（淋巴管密度，LVD）的百分比来测量。多因素分析各HuR表达与临床病理特征、预后、考克斯-2和VEGF表达的关系。在10只N-丁基-N-[4-羟基丁基]亚硝胺（BBN）诱发的小鼠膀胱癌模型中检测了HuR的表达。在人体组织中，分别在5%和25.4%的正常细胞和癌细胞中观察到高细胞质表达。核HuR表达与任何病理特征均无显著相关性。胞浆HuR表达与pT分期、分级呈正相关（P<0.001）。在小鼠组织中，证实了类似的趋势。细胞质表达与PI、MVD和LVD以及VEGF-A和-C的表达相关，但与VEGF-D无关。HuR的高细胞质表达是转移和病因特异性生存的重要预测因子，在包括病理特征的多变量分析模型中，HuR的高细胞质表达被确定为转移的预后相关因素（风险比，4.75; P = 0.028）。 细胞质HuR似乎在膀胱癌患者的细胞增殖、进展和存活中起重要作用。其表达与血管生成、淋巴管生成及VEGF-A和-C的表达有关。
Human antigen R (HuR) regulates the stability of mRNA and is associated with cell proliferation, angiogenesis, and lymphangiogenesis. However, the clinical significance and pathological role of HuR in bladder cancer remains unclear. The main objective of this investigation was to clarify the relationships between HuR expression and clinical significance and cancer cell proliferation, angiogenesis, lymphangiogenesis, and expressions of cyclooxygenase (COX)-2 and vascular endothelial growth factor (VEGF)-A, -C, and -D. All expressions were examined by immunohistochemical techniques in 122 formalin-fixed specimens of bladder cancer patients. HuR expression was evaluated separately with cytoplasmic and nuclear staining. Cell proliferation, angiogenesis and lymphangiogenesis were measured as the percentage of Ki-67-positive cell (proliferation index, PI), CD34-stained vessels (microvessel density, MVD), and D2-40-stained vessels (lymph vessel density, LVD). Relationships between each HuR expression and clinicopathological features, prognosis, and expressions of COX-2 and VEGFs were analyzed by multi-variate analyses. HuR expression was also investigated in 10 mice of N-Butyl-N-[4-hydroxybutil] nitrosamine (BBN) induced bladder cancer model. In human tissues, high cytoplasmic expression was seen in 5% and 25.4% of normal and cancer cells, respectively. Nuclear HuR expression bore no significant relationship to any pathological features. However, cytoplasmic HuR expression appeared positively associated with pT stage and grade (P<0.001). In mouse tissues, similar trends were confirmed. Cytoplasmic expression correlated with PI, MVD, and LVD, as well as expression of VEGF-A and -C, but not VEGF-D. High cytoplasmic expression of HuR was a significant predictor of metastasis and cause-specific survival, and was identified as a prognostic correlative factor for metastasis (hazard ratio, 4.75; P = 0.028) in a multivariate analysis model that included pathological features. Cytoplasmic HuR appears to play important roles in cell proliferation, progression, and survival of bladder cancer patients. Its expression was associated with angiogenesis, lymphangiogenesis, and expressions of VEGF-A and –C.
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影响因子：
6.6
作者：
Shariat, SF;Matsumoto, K;Lerner, SP
通讯作者：
Lerner, SP
影响因子：
3.5
作者：
Wang, Jun;Zhao, Weipeng;Chen, Zhengtang
通讯作者：
Chen, Zhengtang
影响因子：
14.9
作者：
Kim I;Kwak H;Lee HK;Hyun S;Jeong S
通讯作者：
Jeong S
DOI：
10.2741/3921
发表时间：
2012-01-01
期刊：
Frontiers in bioscience (Landmark edition)
影响因子：
--
作者：
Srikantan S;Gorospe M
通讯作者：
Gorospe M
影响因子：
11.5
作者：
Miyata, Y;Kanda, S;Kanetake, H
通讯作者：
Kanetake, H