High-level expression of ARID1A predicts a favourable outcome in triple-negative breast cancer patients receiving paclitaxel-based chemotherapy

ARID1A 高水平表达预示接受紫杉醇化疗的三阴性乳腺癌患者将获得良好结果

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作者:Yuan-Feng Lin, Ing-Jy Tseng, Chih-Jung Kuo, Hui-Yu Lin, I-Jen Chiu, Hui-Wen Chiu

Abstract

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 IC50 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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