Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Surgery, Beijing Cancer Hospital & Institute, Peking University School of Oncology, Beijing, China.
Ann Surg Oncol. 2010 Oct;17(10):2628-39. doi: 10.1245/s10434-010-1037-9. Epub 2010 Apr 10.
The endothelial cell-specific molecule-1 (ESM-1) gene is involved in various biological events. This study was designed to clarify its clinical significance and explore its biological behavior in gastric cancer (GC).
ESM-1 mRNA expression was evaluated by real-time PCR in GC (n = 34) and matched adjacent normal tissues (n = 14). The expression of ESM-1 protein was investigated by immunohistochemistry in GC (n = 159) and matched normal tissues (n = 40), and its correlation with the clinicopathological features and overall survival of patients was analyzed. Microvessel density (MVD) in GC was assessed by anti-CD34 and the pattern of ESM-1 expression in tumor-related vascular was evaluated. The effect of ESM-1 promotion of proliferation in the GC MKN28 cell line and human microvascular endothelial cell line HMEC-1 were tested using the MTT assay.
ESM-1 mRNA was significantly overexpressed in GC compared with adjacent noncarcinoma controls (P < 0.01). ESM-1 protein was predominantly expressed in GC. ESM-1 expression was associated with distant metastasis and Borrmann type IV (P < 0.05) and was strongly associated with vascular invasion (P = 0.0057). Patients with ESM-1 expression showed lower 5-year survival rate (P = 0.0339). Multivariate analysis revealed that ESM-1 was an independent prognostic factor. In GC, CD34-MVD of GC vessels positively expressing ESM-1 was higher than that of GC with negative vessels expression of ESM-1 (P < 0.05). Besides, ESM-1 antibody dose-dependently impaired MKN28 and HMEC-1 growth.
ESM-1 is overexpressed in GC and can serve as a tumor biomarker to predict survival of GC patients, and it might promote tumor angiogenesis and growth in GC and, hence, may represent a potential therapeutic target.
内皮细胞特异性分子-1（ESM-1）基因参与多种生物学事件。本研究旨在阐明其临床意义，并探讨其在胃癌（GC）中的生物学行为。
通过实时 PCR 评估 GC（n=34）和匹配的相邻正常组织（n=14）中的 ESM-1 mRNA 表达。通过免疫组织化学法检测 GC（n=159）和匹配的正常组织（n=40）中 ESM-1 蛋白的表达，并分析其与患者临床病理特征和总生存的相关性。通过抗-CD34 评估 GC 中的微血管密度（MVD），并评估肿瘤相关血管中 ESM-1 表达的模式。通过 MTT 测定法测试 ESM-1 促进 GC MKN28 细胞系和人微血管内皮细胞系 HMEC-1 增殖的作用。
与相邻非癌对照相比，GC 中 ESM-1 mRNA 表达显著上调（P<0.01）。ESM-1 蛋白在 GC 中主要表达。ESM-1 表达与远处转移和 Borrmann 型 IV（P<0.05）相关，与血管侵犯强烈相关（P=0.0057）。ESM-1 表达的患者 5 年生存率较低（P=0.0339）。多变量分析显示 ESM-1 是独立的预后因素。在 GC 中，ESM-1 阳性表达的 GC 血管 CD34-MVD 高于 ESM-1 阴性表达的 GC 血管（P<0.05）。此外，ESM-1 抗体剂量依赖性地损害了 MKN28 和 HMEC-1 的生长。
ESM-1 在 GC 中过度表达，可作为预测 GC 患者生存的肿瘤标志物，它可能促进 GC 中的肿瘤血管生成和生长，因此可能代表一个潜在的治疗靶点。
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