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前列腺癌中预后不良标志物的过度表达:AQP5 促进细胞生长和局部浸润。

Over-expression of a poor prognostic marker in prostate cancer: AQP5 promotes cells growth and local invasion.

机构信息

Department of Urology, the Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi Province 710004, China.

出版信息

World J Surg Oncol. 2014 Sep 13;12:284. doi: 10.1186/1477-7819-12-284.

DOI:10.1186/1477-7819-12-284
PMID:25217331
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4247740/
Abstract

BACKGROUND

The aquaporins (AQPs), water channel proteins, are known playing a major role in transcellular and transepithelial water movement; they also exhibit several properties related to tumor development. The aim of the present study is to elucidate whether the expression of AQP5 is a strong prognostic biomarker for prostate cancer, and the potential role in the progression of prostate cancer cells.

METHODS

AQP5 expression was measured in 60 prostate cancer tissues and cells (both PC-3 and LNCaP) by immunohistochemistry and immunofluorescence assay. AQP5 gene amplification was detected with FISH (fluorescence in situ hybridization). Proliferation and migration of cells and AQP5 siRNA cells were detected with MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) and Boyden chambers. Circulating tumor cells (CTCs) were detected by imFISH staining (CEP8-CD45-DAPI) assay.

RESULTS

The results showed that in 60 tumor specimens, 19 (31.7%) patients showed high level of AQP5 expression, while 30 (50.0%) showed a moderate, intermediate level of staining, and 11 (18.3%) showed an absence of AQP5 staining, respectively. High-expression of AQP5 protein frequently accompanied gene amplification detection with FISH. The AQP5 over-expression was also associated with TNM stage (P=0.042), and lymph node metastasis (P=0.001). The relationships between age or tumor size with the expression of AQP5 were not significant (P>0.05). A positive correlation between the number of CTCs and AQP5 expression (P<0.05) was demonstrated. In addition, patients who were negative for AQP5 had superior cumulative survival rate than those who were positive for it. Over-expression of AQP5 protein was also found in prostate cancer cells and cell proliferation and migration were significantly attenuated by AQP5-siRNA.

CONCLUSIONS

We concluded that AQP5 in prostate cancer was an independent prognostic indicator. AQP5 over-expression was likely to play a role in cell growth and metastasis. These conclusions suggest that AQP5 may be an effective therapeutic target for prostate cancer.

摘要

背景

水通道蛋白(AQPs)是一种已知的在细胞间和上皮细胞间水运动中起主要作用的水通道蛋白,它们还表现出与肿瘤发展相关的多种特性。本研究旨在阐明 AQP5 的表达是否是前列腺癌的一个强有力的预后生物标志物,以及其在前列腺癌细胞进展中的潜在作用。

方法

通过免疫组织化学和免疫荧光分析测量 60 例前列腺癌组织和细胞(PC-3 和 LNCaP)中 AQP5 的表达。用 FISH(荧光原位杂交)检测 AQP5 基因扩增。用 MTT(3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴盐)和 Boyden 室检测细胞增殖和迁移,用 imFISH 染色(CEP8-CD45-DAPI)检测循环肿瘤细胞(CTC)。

结果

结果显示,在 60 个肿瘤标本中,19 例(31.7%)患者 AQP5 表达水平高,30 例(50.0%)表达水平中等,11 例(18.3%)表达水平缺失。AQP5 蛋白的高表达常伴有 FISH 检测到的基因扩增。AQP5 的过表达也与 TNM 分期(P=0.042)和淋巴结转移(P=0.001)有关。AQP5 表达与年龄或肿瘤大小之间的关系不显著(P>0.05)。还证明了 CTC 数量与 AQP5 表达之间存在正相关(P<0.05)。此外,AQP5 阴性的患者累积生存率优于 AQP5 阳性的患者。AQP5 蛋白的过表达也存在于前列腺癌细胞中,AQP5-siRNA 显著抑制了细胞增殖和迁移。

结论

我们得出结论,AQP5 在前列腺癌中是一个独立的预后指标。AQP5 的过表达可能在细胞生长和转移中起作用。这些结论表明,AQP5 可能是治疗前列腺癌的有效靶点。

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