1] Cardiff University-Peking University School of Oncology Joint Institute, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK [2] Metastasis and Angiogenesis Research Group, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK [3] Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery, Peking University Cancer Hospital and Institute, No. 52, Haidian District, Beijing 100142, China.
1] Cardiff University-Peking University School of Oncology Joint Institute, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK [2] Metastasis and Angiogenesis Research Group, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK.
Br J Cancer. 2014 Jan 21;110(2):421-9. doi: 10.1038/bjc.2013.712. Epub 2013 Dec 3.
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.
DAP3 是死亡相关蛋白(DAP)家族的成员,其特征是具有促凋亡功能。它参与了外源性和内源性凋亡途径。在我们之前的研究中,凋亡水平与术前化疗的效果相关。术前化疗的效果也与联合治疗的整体效果和预后相关。本研究旨在探讨 DAP3 在评估术前化疗效果及其预测胃癌预后中的作用。
对 87 例接受联合治疗的患者进行定量 PCR 和免疫组织化学染色。在胃癌细胞系中敲低 DAP3,以研究其对细胞生长、迁移、黏附和侵袭的影响。通过评估细胞凋亡和半胱氨酸天冬氨酸蛋白酶-3(caspase-3)来确定对化疗药物的耐受性。
胃肿瘤中 DAP3 表达较高与预后较好相关。敲低 DAP3 表达可促进细胞迁移,并通过抑制细胞凋亡来增强对化疗的耐药性。
DAP3 是预测接受新辅助化疗和胃切除术的胃癌患者对术前化疗反应和预后的潜在分子标志物。