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Death-associated protein-3, DAP-3, correlates with preoperative chemotherapy effectiveness and prognosis of gastric cancer patients following perioperative chemotherapy and radical gastrectomy
Authors:Y Jia  L Ye  K Ji  L Zhang  R Hargest  J Ji  W G Jiang
Institution: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
Abstract:

Background:

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.

Methods:

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.

Results:

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.

Conclusion:

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.
Keywords:gastric cancer  neoadjuvant chemotherapy  apoptosis  DAP3  effectiveness
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