Wu Nandie, Huang Ying, Zou Zhengyun, Gimenez-Capitan Ana, Yu Lixia, Hu Wenjing, Zhu Lijing, Sun Xia, Sanchez Jose Javier, Guan Wenxian, Liu Baorui, Rosell Rafael, Wei Jia
The Comprehensive Cancer Centre of Drum Tower Hospital, Department of Oncology, The Affiliated Drum Tower Hospital of Nanjing University, Medical School of Nanjing University, Clinical Cancer Institute of Nanjing University, Nanjing, Jiangsu 210008, P.R. China.
Pangaea Biotech, Department of Oncology, USP Dexeus University Institute, Barcelona 08001, Spain.
Oncol Lett. 2017 Mar;13(3):1826-1834. doi: 10.3892/ol.2017.5660. Epub 2017 Feb 1.
Chemotherapy drugs, including 5-fluorouracil (5-FU), oxaliplatin and docetaxel, are commonly used in the treatment of gastric cancer (GC). Apoptosis-relevant genes may be associated with drug resistance. In the present study, the messenger RNA (mRNA) expression levels of B-cell lymphoma 2 interacting mediator of cell death (BIM), astrocyte elevated gene-1 (AEG-1) and AXL receptor tyrosine kinase (AXL) were investigated in 131 advanced GC samples, and the expression levels of these genes were correlated with patients' overall survival (OS). All 131 patients received first-line FOLFOX combination chemotherapy with folinic acid and 5-FU, in which 56 patients were further treated with second-line docetaxel-based chemotherapy. A correlation between the mRNA expression levels of BIM and AEG-1 was observed (=0.30; P=0.002). There was no association between the mRNA expression levels of any of the individual genes analyzed and OS in patients only receiving first-line FOLFOX chemotherapy. In a subgroup of patients receiving docetaxel-based second-line chemotherapy, those with high or intermediate levels of BIM exhibited a median OS of 18.2 months [95% confidence interval (CI), 12.8-23.6], compared with 9.6 months (95% CI, 8.9-10.3) in patients with low BIM levels (P=0.008). However, there was no correlation between the mRNA expression levels of AEG-1 or AXL and OS. The risk of mortality was higher in patients with low BIM mRNA levels than in those with high or intermediate BIM mRNA levels (hazard ratio, 2.61; 95% CI, 1.21-5.62; P=0.010). Therefore, BIM may be considered as a biomarker to identify whether patients could benefit from docetaxel-based second-line chemotherapy in GC.
化疗药物，包括5-氟尿嘧啶（5-FU）、奥沙利铂和多西他赛，常用于治疗胃癌（GC）。凋亡相关基因可能与耐药性有关。在本研究中，对131例晚期GC样本中细胞死亡的B细胞淋巴瘤2相互作用介质（BIM）、星形胶质细胞升高基因-1（AEG-1）和AXL受体酪氨酸激酶（AXL）的信使核糖核酸（mRNA）表达水平进行了研究，并且这些基因的表达水平与患者的总生存期（OS）相关。所有131例患者均接受了含亚叶酸和5-FU的一线FOLFOX联合化疗，其中56例患者进一步接受了以多西他赛为基础的二线化疗。观察到BIM和AEG-1的mRNA表达水平之间存在相关性（=0.30；P=0.002）。在仅接受一线FOLFOX化疗的患者中，所分析的任何单个基因的mRNA表达水平与OS之间均无关联。在接受以多西他赛为基础的二线化疗的患者亚组中，BIM水平高或中等的患者的中位OS为18.2个月[95%置信区间（CI），12.8-23.6]，而BIM水平低的患者为9.6个月（95%CI，8.9-10.3）（P=0.008）。然而，AEG-1或AXL的mRNA表达水平与OS之间无相关性。BIM mRNA水平低的患者的死亡风险高于BIM mRNA水平高或中等的患者（风险比，2.61；95%CI，1.21-5.62；P=0.010）。因此，BIM可被视为一种生物标志物，用于识别GC患者是否能从以多西他赛为基础的二线化疗中获益。
