Yue Wen-Jing, Liu Yi-Pin, Li Ming, Liu Cheng-Xia, Mou Shao-Jia, Li Qian-Kun, Chen Zi-Ping
Department of Gastroenterology, The Qianfoshan Hospital of Shandong University, Jinan, Shandong 250014, P.R. China.
Department of Gastroenterology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong 264003, P.R. China.
Oncol Lett. 2018 Oct;16(4):4455-4461. doi: 10.3892/ol.2018.9202. Epub 2018 Jul 24.
Gastric cancer is an intractable disease with a poor prognosis and limited treatment options. Its treatment remains a major clinical challenge worldwide. Ephrin-B2 is upregulated and involved in tumor growth in various types of cancer. However, the association between ephrin-B2 and prognosis of gastric cancer, and the potential of ephrin-B2 as a therapeutic target remains unknown. The present study investigated ephrin-B2 as a prognostic factor and a therapeutic target for gastric cancer. Reverse transcription-quantitative polymerase chain reaction was performed to detect the protein expression level of ephrin-B2 in gastric cancer serum samples (n=162) and healthy serum samples (n=165). It was revealed that the protein expression level of ephrin-B2 was significantly upregulated in gastric cancer serum samples compared with the healthy samples. Ephrin-B2 protein expression was associated with tumor size (P<0.001), metastasis (P=0.02) and TNM stage (P=0.03), and was indicated to be an independent prognostic factor for gastric cancer. Furthermore, the Kaplan-Meier survival curve demonstrated that patients with high ephrin-B2 protein expression had shorter overall and progression-free survival rates than those with low ephrin-B2 protein expression. Ephrin-B2 protein expression was induced by small interfering RNA (siRNA) transfection of HGC27 and MKN-45 cells, significantly impeding cell viability and inducing apoptosis of HGC27 and MKN-45 cells compared with the respective negative control (NC) group. Thus, to the best of our knowledge, the present study indicates that ephrin-B2 functions as an oncogene in gastric cancer, and that serum ephrin-B2 level may be a promising non-invasive prognostic indicator, as well as a therapeutic target for gastric cancer.
胃癌是一种难治性疾病，预后较差且治疗选择有限。其治疗仍是全球主要的临床挑战。Ephrin-B2在多种类型的癌症中上调并参与肿瘤生长。然而，Ephrin-B2与胃癌预后之间的关联以及Ephrin-B2作为治疗靶点的潜力仍不清楚。本研究调查了Ephrin-B2作为胃癌的预后因素和治疗靶点。采用逆转录定量聚合酶链反应检测胃癌血清样本（n=162）和健康血清样本（n=165）中Ephrin-B2的蛋白表达水平。结果显示，与健康样本相比，胃癌血清样本中Ephrin-B2的蛋白表达水平显著上调。Ephrin-B2蛋白表达与肿瘤大小（P<0.001）、转移（P=0.02）和TNM分期（P=0.03）相关，表明是胃癌的独立预后因素。此外，Kaplan-Meier生存曲线表明，Ephrin-B2蛋白高表达患者的总生存率和无进展生存率低于Ephrin-B2蛋白低表达患者。通过小干扰RNA（siRNA）转染HGC27和MKN-45细胞诱导Ephrin-B2蛋白表达，与各自的阴性对照（NC）组相比，显著抑制HGC27和MKN-45细胞的活力并诱导其凋亡。因此，据我们所知，本研究表明Ephrin-B2在胃癌中起癌基因作用，血清Ephrin-B2水平可能是一种有前景的非侵入性预后指标以及胃癌的治疗靶点。
