Death-associated protein-3, DAP-3, correlates with preoperative chemotherapy effectiveness and prognosis of gastric cancer patients following perioperative chemotherapy and radical gastrectomy.

Death-associated protein-3, DAP-3, correlates with preoperative chemotherapy effectiveness and prognosis of gastric cancer patients following perioperative chemotherapy and radical gastrectomy.
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DOI:
10.1038/bjc.2013.712
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发表时间:
2014-01-21
影响因子:
8.8
通讯作者:
Jiang, W. G.
Jiang, W. G.
中科院分区:
医学1区
文献类型:
--
作者:
Jia, Y.;Ye, L.;Ji, K.;Zhang, L.;Hargest, R.;Ji, J.;Jiang, W. G.

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DAP 3是死亡相关蛋白(DAP)家族的成员,其特征在于促凋亡功能。它参与外源性和内源性凋亡途径。在我们以前的研究中,发现凋亡水平与术前化疗的有效性相关。术前化疗的有效性也与综合治疗的总体疗效和预后有关。本研究旨在探讨DAP 3在胃癌术前化疗疗效评价及预后预测中的作用。对87例接受联合治疗的患者进行定量PCR和免疫组化染色。在胃癌细胞系中进行DAP 3的敲除以研究其对细胞生长、迁移、粘附和侵袭的影响。通过评估细胞凋亡和caspase-3来确定对化疗剂的耐受性。胃肿瘤中较高的DAP 3表达与较好的预后相关。DAP 3表达的敲低促进细胞迁移,并通过抑制凋亡增强对化疗的抵抗。DAP 3是一个潜在的分子标志物,可用于胃癌患者术前化疗反应和预测新辅助化疗和胃切除术后的预后。
DAP3 is a member of the death-associated protein (DAP) family and is characterised by proapoptotic function. It is involved in both exogenous and endogenous apoptotic pathways. In our previous studies, apoptotic level was found to be correlated with the effectiveness of preoperative chemotherapy. The effectiveness of preoperative chemotherapy was also associated with the overall effectiveness of the combined therapy and prognosis. The present study aimed to investigate the role of DAP3 in the evaluation of preoperative chemotherapy effectiveness and its ability to predict prognosis in gastric cancer. Quantitative PCR and immunohistochemistry staining were performed in 87 patients who received combined therapy. Knockdown of DAP3 was conducted in gastric cancer cell lines to investigate its impact on cell growth, migration, adhesion and invasion. Tolerance to chemotherapy agents was determined by assessing apoptosis and caspase-3. Higher DAP3 expression in gastric tumours was correlated with better prognosis. Knockdown of DAP3 expression promoted cell migration and enhanced resistance to chemotherapy by inhibiting apoptosis. DAP3 is a potential molecular marker for response to preoperative chemotherapy and for predicting prognosis in gastric cancer patients treated with neoadjuvant chemotherapy and gastrectomy.
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