Molecular and Clinical Relevance of ZBTB38 Expression Levels in Prostate Cancer
Molecular and Clinical Relevance of ZBTB38 Expression Levels in Prostate Cancer
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DOI：
10.3390/cancers12051106
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发表时间：
2020-05-01
期刊：
影响因子：
5.2
通讯作者：
Miotto, Benoit
中科院分区：
文献类型：
--
作者：
de Dieuleveult, Maud;Marchal, Claire;Miotto, Benoit
前列腺癌是男性最常诊断的癌症之一。许多基因组和临床研究使人们更好地了解前列腺癌生物学。尽管如此，患者的护理以及疾病侵袭性、复发和结果的预测仍然具有挑战性。在这里，我们发现基因 ZBTB38 的表达与局限性前列腺癌的不良预后相关，并且可以帮助区分侵袭性局限性前列腺肿瘤和那些只能从观察中获益的肿瘤。对不同前列腺癌队列的分析表明，ZBTB38 的低表达水平与染色体异常水平增加和更具侵袭性的病理特征相关，包括较高的疾病生化复发率。重要的是，这些肿瘤的基因表达谱与前列腺癌细胞系的细胞分析相结合，揭示了低水平 ZBTB38 表达的肿瘤可能是阿霉素（一种产生活性氧的化合物）的靶标。我们的研究表明，ZBTB38 参与前列腺癌发病机制，并且可能是识别对阿霉素敏感的高风险和高度重排的局限性前列腺癌的有用标记。
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 ZBTB38 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 ZBTB38 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 ZBTB38 expression might be targeted by doxorubicin, a compound generating reactive oxygen species. Our study shows that ZBTB38 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.