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前列腺癌中表达水平的分子与临床相关性

Molecular and Clinical Relevance of Expression Levels in Prostate Cancer.

作者信息

de Dieuleveult Maud, Marchal Claire, Jouinot Anne, Letessier Anne, Miotto Benoit

机构信息

Team Epigenetics, DNA replication and Cancer, Université de Paris, Institut Cochin, INSERM, F-75014 Paris, France.

Neurobiology, Neurodegeneration & Repair Laboratory, National Eye Institute, National Institutes of Health, MSC0610, 6 Center Drive, Bethesda, MD 20892, USA.

出版信息

Cancers (Basel). 2020 Apr 29;12(5):1106. doi: 10.3390/cancers12051106.

Abstract

Prostate cancer is one of the most commonly diagnosed cancers in men. A number of genomic and clinical studies have led to a better understanding of prostate cancer biology. Still, the care of patients as well as the prediction of disease aggressiveness, recurrence and outcome remain challenging. Here, we showed that expression of the gene is associated with poor prognosis in localised prostate cancer and could help discriminate aggressive localised prostate tumours from those who can benefit only from observation. Analysis of different prostate cancer cohorts indicates that low expression levels of associate with increased levels of chromosomal abnormalities and more aggressive pathological features, including higher rate of biochemical recurrence of the disease. Importantly, gene expression profiling of these tumours, complemented with cellular assays on prostate cancer cell lines, unveiled that tumours with low levels of expression might be targeted by doxorubicin, a compound generating reactive oxygen species. Our study shows that is involved in prostate cancer pathogenesis and may represent a useful marker to identify high risk and highly rearranged localised prostate cancer susceptible to doxorubicin.

摘要

前列腺癌是男性中最常被诊断出的癌症之一。许多基因组和临床研究使人们对前列腺癌生物学有了更好的理解。然而,患者的护理以及疾病侵袭性、复发和预后的预测仍然具有挑战性。在此,我们表明该基因的表达与局限性前列腺癌的不良预后相关,并且有助于区分侵袭性局限性前列腺肿瘤与那些仅能从观察中获益的肿瘤。对不同前列腺癌队列的分析表明,该基因低表达水平与染色体异常水平升高以及更具侵袭性的病理特征相关,包括疾病更高的生化复发率。重要的是,这些肿瘤的基因表达谱分析,辅以对前列腺癌细胞系的细胞实验,揭示出该基因低表达水平的肿瘤可能对阿霉素敏感,阿霉素是一种产生活性氧的化合物。我们的研究表明该基因参与前列腺癌的发病机制,并且可能是识别对阿霉素敏感的高危和高度重排的局限性前列腺癌的有用标志物。

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