High-level expression of ARID1A predicts a favourable outcome in triple-negative breast cancer patients receiving paclitaxel-based chemotherapy.
High-level expression of ARID1A predicts a favourable outcome in triple-negative breast cancer patients receiving paclitaxel-based chemotherapy.
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DOI：
10.1111/jcmm.13551
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发表时间：
2018-04
影响因子：
5.3
通讯作者：
Chiu HW
中科院分区：
文献类型：
--
作者：
Lin YF;Tseng IJ;Kuo CJ;Lin HY;Chiu IJ;Chiu HW
基于紫杉醇的化疗是治疗三阴性乳腺癌（TNBC）患者的常用策略。由于紫杉醇耐药性仍然是治疗TNBC的临床问题，因此迫切需要鉴定用于预测对紫杉醇治疗的病理反应的分子标志物。在这里，我们报告了富含AT的相互作用结构域1A（ARID 1A）转录物在紫杉醇敏感的TNBC细胞中上调，但在紫杉醇治疗后的紫杉醇耐药细胞中下调。此外，在测试的TNBC细胞系中，ARID 1A表达与紫杉醇的IC 50浓度负相关。Kaplan-Meier分析显示，ARID 1A下调与TNBC患者对基于紫杉醇的化疗的反应较差有关，如无复发生存概率所测量的。用p38 MAPK特异性抑制剂Scio-469进行的药物抑制揭示了p38 MAPK相关信号传导轴调节ARID 1A表达，从而调节TNBC细胞中的紫杉醇敏感性。这些发现表明，ARID 1A可用作预后因素，以估计决定接受紫杉醇化疗的TNBC患者的病理完全缓解。
Paclitaxel‐based chemotherapy is a common strategy to treat patients with triple‐negative breast cancer (TNBC). As paclitaxel resistance is still a clinical issue in treating TNBCs, identifying molecular markers for predicting pathologic responses to paclitaxel treatment is thus urgently needed. Here, we report that an AT‐rich interaction domain 1A (ARID1A) transcript is up‐regulated in paclitaxel‐sensitive TNBC cells but down‐regulated in paclitaxel‐resistant cells upon paclitaxel treatment. Moreover, ARID1A expression was negatively correlated with the IC 50 concentration of paclitaxel in the tested TNBC cell lines. Kaplan‐Meier analyses revealed that ARID1A down‐regulation was related to a poorer response to paclitaxel‐based chemotherapy in patients with TNBCs as measured by the recurrence‐free survival probability. The pharmaceutical inhibition with p38MAPK‐specific inhibitor SCIO‐469 revealed that p38MAPK‐related signalling axis regulates ARID1A expression and thereby modulates paclitaxel sensitivity in TNBC cells. These findings suggest that ARID1A could be used as a prognostic factor to estimate the pathological complete response for TNBC patients who decide to receive paclitaxel‐based chemotherapy.
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影响因子：
28.2
作者：
Shen J;Peng Y;Wei L;Zhang W;Yang L;Lan L;Kapoor P;Ju Z;Mo Q;Shih IeM;Uray IP;Wu X;Brown PH;Shen X;Mills GB;Peng G
通讯作者：
Peng G
影响因子：
8
作者：
de la Cruz-Morcillo, M. A.;Valero, M. L. L.;Sanchez-Prieto, R.
通讯作者：
Sanchez-Prieto, R.
影响因子：
3.6
作者：
McDaid, HM;Horwitz, SB
通讯作者：
Horwitz, SB
影响因子：
8
作者：
Mamo, A.;Cavallone, L.;Basik, M.
通讯作者：
Basik, M.
用于管理三阴性转移性乳腺癌的NAB-甲酰胺：一个案例研究。
影响因子：
2.3
作者：
Arpino G;De Placido S;De Angelis C
通讯作者：
De Angelis C