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前列腺癌中缺氧相关基因表达分析:赖氨酰氧化酶和葡萄糖转运蛋白-1表达与 Gleason 评分相关。

Analysis of hypoxia-associated gene expression in prostate cancer: lysyl oxidase and glucose transporter-1 expression correlate with Gleason score.

作者信息

Stewart Grant D, Gray Kelly, Pennington Caroline J, Edwards Dylan R, Riddick Antony C P, Ross James A, Habib Fouad K

机构信息

Prostate Research Group, Edinburgh Cancer Research Centre, School of Molecular and Clinical Medicine, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, UK.

出版信息

Oncol Rep. 2008 Dec;20(6):1561-7.

Abstract

Prostate cancer cells exist under hypoxic conditions. Hypoxia has a detrimental effect on the efficacy of treatment and final outcome in patients with prostate cancer. There have been a large number of endogenous markers of hypoxia described previously across a range of cancer types, both in vitro and in vivo. The aim of this study was to evaluate the expression of a range of hypoxia-associated genes within benign prostatic hypertrophy (BPH) and prostate cancer tissue. Messenger RNA was extracted from primary prostate tissue obtained from 67 men with benign prostatic hypertrophy or prostate cancer (Gleason score 5 to 10). Real-time polymerase chain reaction was performed to quantify the expression levels of 12 hypoxia-associated genes in these tissues. Expression of lysyl oxidase (LOX) and glucose transporter-1 (GLUT-1) genes were significantly higher in prostate cancer compared with BPH tissue (P<0.05) and correlated with Gleason score (LOX: R=0.297, P=0.015; GLUT-1: R=0.274, P=0.026). HIF-2alpha had a negative correlation with Gleason score (R= -0.309, P=0.012). The remaining hypoxia-associated genes did not show any specific pattern of expression in prostate tissue. Numerous molecules have been proposed as endogenous markers of hypoxia. The findings of this study illustrate that not all hypoxia-associated molecules are relevant to prostate cancer in vivo. However, LOX and GLUT-1 are candidate markers of hypoxia in prostate cancer and may prove useful in identifying patients with hypoxic prostate cancer. Not all hypoxia-associated molecules are relevant in prostate cancer in vivo.

摘要

前列腺癌细胞处于缺氧状态。缺氧对前列腺癌患者的治疗效果和最终预后具有不利影响。此前,在一系列癌症类型中,无论是体外还是体内,都已描述了大量缺氧的内源性标志物。本研究的目的是评估一系列缺氧相关基因在良性前列腺增生(BPH)和前列腺癌组织中的表达情况。从67名患有良性前列腺增生或前列腺癌( Gleason评分5至10)的男性获取的原发性前列腺组织中提取信使核糖核酸。进行实时聚合酶链反应以量化这些组织中12种缺氧相关基因的表达水平。与BPH组织相比,赖氨酰氧化酶(LOX)和葡萄糖转运蛋白-1(GLUT-1)基因在前列腺癌中的表达显著更高(P<0.05),且与Gleason评分相关(LOX:R=0.297,P=0.015;GLUT-1:R=0.274,P=0.026)。缺氧诱导因子-2α(HIF-2α)与Gleason评分呈负相关(R=-0.309,P=0.012)。其余缺氧相关基因在前列腺组织中未显示出任何特定的表达模式。许多分子已被提议作为缺氧的内源性标志物。本研究结果表明,并非所有缺氧相关分子在体内都与前列腺癌相关。然而,LOX和GLUT-1是前列腺癌缺氧的候选标志物,可能有助于识别缺氧性前列腺癌患者。并非所有缺氧相关分子在前列腺癌体内都相关。

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