Overexpression of O-GlcNAc by prostate cancer cells is significantly associated with poor prognosis of patients
Overexpression of O-GlcNAc by prostate cancer cells is significantly associated with poor prognosis of patients
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DOI：
10.1038/pcan.2013.56
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发表时间：
2014-03-01
影响因子：
4.8
通讯作者：
Nakayama, J.
中科院分区：
文献类型：
--
作者：
Kamigaito, T.;Okaneya, T.;Nakayama, J.
背景技术背景：O-连接的β-N-乙酰葡糖胺（O-GlcNAc）是一种基本细胞过程所必需的聚糖，如转录/翻译、核转运、蛋白质稳定性和蛋白质-蛋白质相互作用。然而，O-GlcNAc在患者前列腺癌进展中的作用仍然知之甚少。方法：采用免疫组化法检测56例前列腺癌患者经激素剥夺治疗后前列腺活检组织中O-GlcNAc的表达水平，并与同期前列腺组织中正常前列腺组织进行比较。采用Kaplan-Meier和考克斯比例风险法及单变量和多变量模型确定总生存期。O-GlcNAc表达水平降低对前列腺癌LNCaP细胞增殖和侵袭的影响使用靶向O-GlcNAc转移酶（OGT）的小干扰RNA（siRNA）进行检测，O-GlcNAc转移酶是负责O-GlcNAc生物合成的酶。结果：将表现出比正常前列腺更强的细胞质染色的癌细胞定义为O-GlcNAc过表达，39%的前列腺癌患者被归类为过表达。Kaplan-Meier和考克斯比例风险法与单变量模型分析显示，O-GlcNAc过表达与总生存期相关（Kaplan-Meier分析P = 0.0012，考克斯单变量风险模型分析P = 0.0021）。此外，O-GlcNAc是通过多变量分析观察到的总生存期显著差异的唯一项目（P = 0.0475）。最后，siRNA介导的OGT敲低LNCaP细胞导致O-GlcNAc的表达下降，促进降低增殖和肿瘤细胞侵袭相比，控制siRNA转染LNCaP cells.CONCLUSIONS：这些结果表明，O-GlcNAc在前列腺癌细胞中的表达水平与前列腺癌患者的预后不良，并可能增强肿瘤细胞的增殖和侵袭。
BACKGROUND: O-linked beta-N-acetylglucosamine (O-GlcNAc) is a glycan essential for fundamental cellular processes such as transcription/translation, nuclear transport, protein stability and protein-protein interactions. However, the role of O-GlcNAc in prostate cancer progression of patients remains poorly unknown. Here we investigated the clinicopathological significance of O-GlcNAc expression level in prostate cancer.METHODS: O-GlcNAc expression level in prostate cancer cells was determined by immunohistochemistry of prostate biopsy specimens obtained from 56 patients later treated with hormone deprivation therapy comparing with adjacent normal prostate glands in the same sections. Overall survival was determined by the Kaplan-Meier and Cox proportional hazards methods with univariate and multivariate models. The effects of reduced O-GlcNAc expression level on proliferation and invasion of prostate cancer LNCaP cells were examined using small interfering RNA (siRNA) targeting O-GlcNAc transferase (OGT), the enzyme responsible for O-GlcNAc biosynthesis.RESULTS: Defining cancer cells showing stronger cytoplasmic staining than normal prostate glands as overexpression of O-GlcNAc, 39% of prostate cancer patients were categorized as overexpression. The Kaplan-Meier and Cox proportional hazards methods with univariate model analysis revealed that O-GlcNAc overexpression was associated with overall survival (P = 0.0012 for the Kaplan-Meier and P = 0.0021 for Cox univariate hazard model analysis). Furthermore, O-GlcNAc was the only item in which a significant difference was observed at overall survival by multivariate analysis (P = 0.0475). Finally, siRNA-mediated OGT knockdown in LNCaP cells resulted in decreased expression of O-GlcNAc and promoted decreased proliferation and tumor cell invasion compared with control siRNA-transfected LNCaP cells.CONCLUSIONS: These results indicate that O-GlcNAc expression level in prostate cancer cells is associated with poor prognosis of prostate cancer patients and likely enhances tumor cell proliferation and invasion.