School of Medicine, Shandong University, Jinan, Shandong, China (mainland).
Department of Gastrointestinal Oncology Surgery, Anhui Provincial Cancer Hospital (West District of The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China), Hefei, Anhui, China (mainland).
Med Sci Monit. 2020 Mar 27;26:e923409. doi: 10.12659/MSM.923409.
BACKGROUND With the growing global burden of gastric carcinoma (GC) and the urgent need for biomolecular targeted therapies, this study aimed to elucidate the relationship between EphA1 and the tumor microenvironment (focusing primarily on the key inflammatory cytokines IL-6 and tumor angiogenic cytokine VEGF) to identify a new potential therapeutic target. MATERIAL AND METHODS IHC and qRT-PCR were performed to quantify the protein and gene expression levels of EphA1, IL-6, and VEGF in normal mucosal tissues, carcinoma tissues, and paracarcinomatous tissues from 57 GC patients. Spearman's rank correlation test was performed to determine the relationship between EphA1, IL-6, and VEGF expression levels. The relationships of EphA1 with clinicopathologic parameter and survival in GC patients were also evaluated. RESULTS The protein and gene expression levels of EphA1 were all attenuated gradually from carcinoma tissues to paracarcinomatous tissues and then to normal mucosal tissues in GC patients. Additionally, significant correlations between the overexpression of EphA1 with aggressive clinicopathological features and shorter survival time of GC patients were verified. In particular, we found a significant positive correlation between the expression of EphA1 and tumor microenvironment hallmark proteins IL-6 and VEGF in carcinoma tissues and paracarcinomatous tissues. CONCLUSIONS EphA1 can promote the occurrence and development of GC by its selective high expression in cancer tissues and its relationship with malignant clinical features and prognosis of GC patients. The underlying potential mechanism appears to involve enhancement of the tumor microenvironment, which via drives the expression of tumor microenvironment hallmark proteins IL-6 and VEGF.
随着胃癌(GC)全球负担的增加和对生物分子靶向治疗的迫切需求,本研究旨在阐明 EphA1 与肿瘤微环境(主要关注关键炎性细胞因子 IL-6 和肿瘤血管生成细胞因子 VEGF)之间的关系,以确定新的潜在治疗靶点。
对 57 例 GC 患者的正常黏膜组织、癌组织和癌旁组织中 EphA1、IL-6 和 VEGF 的蛋白和基因表达水平进行免疫组化和 qRT-PCR 检测。采用 Spearman 秩相关检验确定 EphA1、IL-6 和 VEGF 表达水平之间的关系。还评估了 EphA1 与 GC 患者临床病理参数和生存的关系。
EphA1 的蛋白和基因表达水平均从癌组织逐渐减弱至癌旁组织,然后在 GC 患者的正常黏膜组织中减弱。此外,EphA1 的过度表达与 GC 患者侵袭性临床病理特征和较短的生存时间之间存在显著相关性。特别是,我们发现 EphA1 在癌组织和癌旁组织中与肿瘤微环境标志性蛋白 IL-6 和 VEGF 的表达呈显著正相关。
EphA1 可通过在癌组织中选择性高表达及其与 GC 患者恶性临床特征和预后的关系,促进 GC 的发生发展。其潜在的潜在机制似乎涉及增强肿瘤微环境,从而促进肿瘤微环境标志性蛋白 IL-6 和 VEGF 的表达。