12-脂氧合酶信使核糖核酸表达升高与人类前列腺癌的晚期阶段及低分化相关。

Elevated 12-lipoxygenase mRNA expression correlates with advanced stage and poor differentiation of human prostate cancer.

作者信息

Gao X, Grignon D J, Chbihi T, Zacharek A, Chen Y Q, Sakr W, Porter A T, Crissman J D, Pontes J E, Powell I J

机构信息

Department of Radiation Oncology, Wayne State University School of Medicine, Harper Hospital, Michigan, USA.

出版信息

Urology. 1995 Aug;46(2):227-37. doi: 10.1016/s0090-4295(99)80198-8.

DOI:10.1016/s0090-4295(99)80198-8

PMID:7624992

Abstract

OBJECTIVES

Prostate cancer is the most frequently diagnosed cancer and the second leading cause of cancer death in males in the United States. The mortality is due mainly to distant metastasis. Therefore, predicting the prognosis of prostate cancer patients is an important clinical problem. Previously, we demonstrated that a 12-lipoxygenase (12-LOX) metabolite of arachidonic acid, 12(S)-hydroxyeicosatetraenoic acid, enhances the invasiveness of prostate cancer cells and that a 12-LOX-selective inhibitor [N-benzyl-N-hydroxy-5-phenylpentanamide] reduces experimental metastasis in animal model systems. In this study, we investigated the potential of 12-LOX as a predictor for the aggressiveness of prostate cancer.

METHODS

The mRNA expression level of 12-LOX in 122 matching prostate normal and cancerous tissues were measured by quantitative reverse transcription- polymerase chain reaction. Possible association between 12-LOX expression and histologic grade, pathologic and clinical stage, margin positivity, age, and race was analyzed.

RESULTS

12-LOX mRNA levels were elevated in cancer cells and the expression associated with poor differentiation and invasiveness of prostate cancer. Overall, 46 (38%) of 122 evaluable patients showed elevated levels of 12-LOX mRNA in prostate cancer tissues compared with the matching normal tissues. A statistically significantly greater number of cases were found to have an elevated level of 12-LOX among T3, high grade, and surgical margin-positive than T2, intermediate, and low grade, and surgical margin-negative prostatic adenocarcinomas.

CONCLUSIONS

Our data suggest that elevation of 12-LOX mRNA expression occurs more frequently in advanced stage, high-grade prostate cancer and that 12-LOX may serve as an indicator for progression and prognosis of prostate cancer. This enzyme also may be a novel target for the development of anti-invasive and antimetastatic agents.

摘要

目的

前列腺癌是美国男性中最常被诊断出的癌症，也是癌症死亡的第二大主要原因。其死亡率主要归因于远处转移。因此，预测前列腺癌患者的预后是一个重要的临床问题。此前，我们证明花生四烯酸的12 -脂氧合酶（12-LOX）代谢产物12(S)-羟基二十碳四烯酸可增强前列腺癌细胞的侵袭性，并且一种12-LOX选择性抑制剂[N-苄基-N-羟基-5-苯基戊酰胺]可减少动物模型系统中的实验性转移。在本研究中，我们调查了12-LOX作为前列腺癌侵袭性预测指标的潜力。

方法

通过定量逆转录-聚合酶链反应测量122对匹配的前列腺正常组织和癌组织中12-LOX的mRNA表达水平。分析12-LOX表达与组织学分级、病理和临床分期、切缘阳性、年龄及种族之间可能的关联。

结果

癌细胞中12-LOX mRNA水平升高，且该表达与前列腺癌的低分化和侵袭性相关。总体而言，122例可评估患者中，有46例（38%）前列腺癌组织中的12-LOX mRNA水平相较于匹配的正常组织升高。在T3期、高级别及手术切缘阳性的前列腺腺癌中，12-LOX水平升高的病例数在统计学上显著多于T2期、中级别及低级别且手术切缘阴性的病例。