LSD1 overexpression is associated with poor prognosis in basal-like breast cancer, and sensitivity to PARP inhibition.
LSD1 overexpression is associated with poor prognosis in basal-like breast cancer, and sensitivity to PARP inhibition.
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DOI：
10.1371/journal.pone.0118002
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Sato K
中科院分区：
文献类型：
--
作者：
Nagasawa S;Sedukhina AS;Nakagawa Y;Maeda I;Kubota M;Ohnuma S;Tsugawa K;Ohta T;Roche-Molina M;Bernal JA;Narváez AJ;Jeyasekharan AD;Sato K
LSD1是一种赖氨酸特异性组蛋白去甲基化酶，在几种类型的癌症中过表达，并与不良结局有关。在乳腺癌中，LSD 1过表达的意义尚不清楚。我们进行了计算机模拟分析，以评估LSD 1表达与临床结局的关系。我们证明LSD 1过表达是乳腺癌预后不良的因素，特别是在基底样乳腺癌，一种具有侵袭性临床特征的乳腺癌亚型。在三阴性乳腺癌样本中也观察到这种联系。有趣的是，我们注意到LSD 1的过表达与三阴性乳腺癌中BRCA 1的下调相关。这种现象也在基底样乳腺癌的体外模型中观察到，并且与对PARP抑制剂的敏感性增加有关。因此，我们认为去甲基化酶LSD 1的高表达水平是基底细胞样乳腺癌预后不良的潜在预后因素，PARP抑制可能是LSD 1过表达的预后不良亚型的治疗策略。
LSD1, a lysine-specific histone demethylase, is overexpressed in several types of cancers and linked to poor outcomes. In breast cancer, the significance of LSD1 overexpression is not clear. We have performed an in silico analysis to assess the relationship of LSD1 expression to clinical outcome. We demonstrate that LSD1 overexpression is a poor prognostic factor in breast cancer, especially in basal-like breast cancer, a subtype of breast cancer with aggressive clinical features. This link is also observed in samples of triple negative breast cancer. Interestingly, we note that overexpression of LSD1 correlates with down-regulation of BRCA1 in triple negative breast cancer. This phenomenon is also observed in in vitro models of basal-like breast cancer, and is associated with an increased sensitivity to PARP inhibitors. We propose therefore that high expression levels of the demethylase LSD1 is a potential prognostic factor of poor outcome in basal-like breast cancer, and that PARP inhibition may be a therapeutic strategy of interest in this poor prognostic subtype with overexpression of LSD1.
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影响因子：
3.1
作者：
Ding Jie;Zhang Zhongmin;Zeng Liang
通讯作者：
Zeng Liang
DOI：
10.1073/pnas.0932692100
发表时间：
2003-07-08
影响因子：
11.1
作者：
Sorlie, T;Tibshirani, R;Botstein, D
通讯作者：
Botstein, D
DOI：
10.1186/bcr1325
发表时间：
2005
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Pawitan Y;Bjöhle J;Amler L;Borg AL;Egyhazi S;Hall P;Han X;Holmberg L;Huang F;Klaar S;Liu ET;Miller L;Nordgren H;Ploner A;Sandelin K;Shaw PM;Smeds J;Skoog L;Wedrén S;Bergh J
通讯作者：
Bergh J
影响因子：
4.7
作者：
Lim, Soyoung;Janzer, Andreas;Kirfel, Jutta
通讯作者：
Kirfel, Jutta
DOI：
10.1007/bf00708323
发表时间：
1986-01-01
期刊：
VIRCHOWS ARCHIV A-PATHOLOGICAL ANATOMY AND HISTOPATHOLOGY
影响因子：
--
作者：
REMMELE, W;HILDEBRAND, U;SCHEIDT, E
通讯作者：
SCHEIDT, E