Song Yan-Yan, Sun Li-Dan, Liu Min-Li, Liu Zhong-Liang, Chen Fei, Zhang Ying-Zhe, Zheng Yan, Zhang Jian-Ping
Department of Pathology, Shandong University School of Medicine, Jinan, Shandong 250012, P.R. China.
Department of Neurosurgery, Yidu Central Hospital, Weifang, Shandong 262500, P.R. China.
Oncol Lett. 2014 Jul;8(1):431-437. doi: 10.3892/ol.2014.2059. Epub 2014 Apr 11.
Vasculogenic mimicry (VM) formation is important for invasion and metastasis of tumor cells in gastric adenocarcinoma (GAC). The present study aimed to investigate the association between signal transducer and activator of transcription-3 (STAT3), phosphor-STAT3 (p-STAT3), hypoxia-inducible factor-1α (HIF-1α) and VM formation in GAC, and discuss their clinical significance and correlation with the prognosis of patients with GAC. The expression levels of STAT3, p-STAT3, HIF-1α and VM were assessed in 60 cases of patients with GAC and 20 cases of patients with gastritis on tissue microarrays by immunohistochemical methods. The expression levels of STAT3, p-STAT3, HIF-1α and VM were higher in patients with GAC (particularly in poorly differentiated GAC) than in those with gastritis (P<0.05). The expression levels of STAT3, p-STAT3 and HIF-1α were higher in VM tissues compared with non-VM tissues (P<0.05). Positive correlations existed between STAT3, p-STAT3, HIF-1α and VM expression (P<0.05). The expression levels of STAT3, p-STAT3 and HIF-1α, VM, status of lymph node metastasis and tumor differentiation degree were associated with the overall survival time of patients with GAC (P<0.05). However, only p-STAT3 and VM expression were identified as the independent risk factors of GAC OS when analyzed with multivariate analysis. p-STAT3 and VM play a significant role in indicating the prognosis of patients with GAC. STAT3 activation may play a positive role in VM formation of GAC by the STAT3-p-STAT3-HIF-1α-VM effect axis.
血管生成拟态（VM）的形成对胃腺癌（GAC）中肿瘤细胞的侵袭和转移具有重要意义。本研究旨在探讨信号转导和转录激活因子3（STAT3）、磷酸化STAT3（p-STAT3）、缺氧诱导因子-1α（HIF-1α）与GAC中VM形成之间的关联，并讨论它们的临床意义以及与GAC患者预后的相关性。采用免疫组织化学方法，在组织芯片上评估60例GAC患者和20例胃炎患者中STAT3、p-STAT3、HIF-1α和VM的表达水平。GAC患者（尤其是低分化GAC患者）中STAT3、p-STAT3、HIF-1α和VM的表达水平高于胃炎患者（P<0.05）。与非VM组织相比，VM组织中STAT3、p-STAT3和HIF-1α的表达水平更高（P<0.05）。STAT3、p-STAT3、HIF-1α与VM表达之间存在正相关（P<0.05）。STAT3、p-STAT3、HIF-1α、VM的表达水平、淋巴结转移状态和肿瘤分化程度与GAC患者的总生存时间相关（P<0.05）。然而，多因素分析时，仅p-STAT3和VM表达被确定为GAC总生存的独立危险因素。p-STAT3和VM在提示GAC患者预后方面起重要作用。STAT3激活可能通过STAT3-p-STAT3-HIF-1α-VM效应轴在GAC的VM形成中发挥积极作用。
