DNA repair genes PAXIP1 and TP53BP1 expression is associated with breast cancer prognosis
DNA repair genes PAXIP1 and TP53BP1 expression is associated with breast cancer prognosis
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DOI：
10.1080/15384047.2017.1323590
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发表时间：
2017-01-01
影响因子：
3.6
通讯作者：
de Carvalho, Marcelo Alex
中科院分区：
文献类型：
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作者：
De Gregoriis, Giuliana;Ramos, Juliene Antonio;de Carvalho, Marcelo Alex
尽管在诊断、预后和治疗方面取得了显著进步，但晚期或复发的乳腺肿瘤的治疗方法有限。许多治疗策略试图探索肿瘤细胞中DNA损伤反应(DDR)的局限性，以选择性地消除它们。BRCT(BRCA1 C-末端)结构域存在于参与细胞周期检查点和DDR的蛋白质超家族中。串联BRCT结构域(TBRCT)代表了这些结构域中的一类。我们研究了7个tBRCT基因(BARD1、BRCA1、LIG4、ECT2、MDC1、PAXIP1/PTIP和TP53BP1)在乳腺癌组织中的表达谱，发现PAXIP1和TP53BP1基因在肿瘤组织中的表达高度相关。预后较差的肿瘤(肿瘤分级3级，三重阴性)，tBRCT基因表达降低，尤其是PAXIP1和TP53BP1。生存分析数据显示，这两个基因的肿瘤状态可能影响预后。PAXIP1和53BP1蛋白水平遵循基因表达结果，即内在相关，在更晚期的肿瘤中也会降低。对BRCA1状态的三阴性乳腺肿瘤样本中这两个基因的评估表明，PAXIP1在BRCA1突变的肿瘤中过度表达。综上所述，我们的发现表明，PAXIP1状态与乳腺癌分期有关，其方式类似于TP53BP1的特征。
Despite remarkable advances in diagnosis, prognosis and treatment, advanced or recurrent breast tumors have limited therapeutic approaches. Many treatment strategies try to explore the limitations of DNA damage response (DDR) in tumor cells to selectively eliminate them. BRCT (BRCA1 C-terminal) domains are present in a superfamily of proteins involved in cell cycle checkpoints and the DDR. Tandem BRCT domains (tBRCT) represent a distinct class of these domains. We investigated the expression profile of 7 tBRCT genes (BARD1, BRCA1, LIG4, ECT2, MDC1, PAXIP1/PTIP and TP53BP1) in breast cancer specimens and observed a high correlation between PAXIP1 and TP53BP1 gene expression in tumor samples. Tumors with worse prognosis (tumor grade 3 and triple negative) showed reduced expression of tBRCT genes, notably, PAXIP1 and TP53BP1. Survival analyses data indicated that tumor status of both genes may impact prognosis. PAXIP1 and 53BP1 protein levels followed gene expression results, i.e., are intrinsically correlated, and also reduced in more advanced tumors. Evaluation of both genes in triple negative breast tumor samples which were characterized for their BRCA1 status showed that PAXIP1 is overexpressed in BRCA1 mutant tumors. Taken together our findings indicate that PAXIP1 status correlates with breast cancer staging, in a manner similar to what has been characterized for TP53BP1.