人胃癌中巨噬细胞金属弹力酶表达与微血管生成的关系

Human macrophage metalloelastase gene expression in angiogenesis and prognostic significance for gastric carcinoma

目的探讨人巨噬细胞金属弹力酶(HME)对胃癌微血管生成及血管内皮生长因子(VEGF)表达的影响,评价其对预后的意义。方法收集术后病理证实胃癌并获得随访,有完整蜡块资料的65例患者,分别进行免疫组化和原位杂交分析,分析 HME 在胃癌组织中的表达与胃癌微血管密度(MVD)及 VEGF 表达之间的关系;通过生存分析及风险模型评估 HME 表达对胃癌预后的影响。结果在胃癌组织中,HME 高表达与肿瘤血管低密度呈显著相关(P<0.01),HME 与 VEGF 表达呈负相关(P<0.01)。影响胃癌组织 MVD 的多因素分析结果表明,HME 及 VEGF 表达均为胃癌组织 MVD 的独立影响因素(P<0.05),HME 表达与 MVD 呈负相关,VEGF 表达与 MVD 呈正相关,HME 表达可作为肿瘤组织 MVD 的预测指标。胃癌术后生存5年以上者 HME 表达率明显高于术后5年内复发死亡者(P<0.05),而 VEGF 表达情况与此相反。影响胃癌预后的多因素分析结果同样显示,HME 高表达者预后较好,VEGF 高表达者预后较差。结论 HME 高表达与胃癌组织低血管密度及较好的预后密切相关,对抑制肿瘤血管形成、提高生存率起重要作用,可能成为预测胃癌 MVD、判断预后的有效指标,而 VEGF表达起着相反的作用,两者间的平衡可能调控着肿瘤中新生血管的生成并因此影响疾病的预后。

Objective The aim of this study is to clarify the role of HME in tumor angiogenesis, and to investigate the association between HME expression and disease progression and prognosis in patients with gastric carcinoma. Methods Patients with primary gastric carcinoma who underwent surgical resection were followed up. HME expression in gastric carcinoma was detected by immunohistochemistry and in situ hybridization for 65 archival paraffin-embedded tissue specimens. The relationship between HME, VEGF and MVD in gastric carcinoma tissue was analyzed. The prognostic significance of HME expression was assessed with Survival analysis and a Cox proportional hazards model. Results In gastric carcinoma tissues, high-level expression of HME was significantly associated with hypovascular tumors （ P 〈0.01 ）. There is inverse correlation between expression of HME and VEGF （ P 〈 0. 01 ）. Multivariate analysis about MVD indicated that HME and VEGF were both independent influence factors （ P 〈0.01 ）, moreover, HME expression may serve as a predictive indicator about MVD of tumor. High-level HME expression rate in the patients who died of cancer recurrence was much lower than the rate in those patients with over 5-years survival after surgery （ P 〈 0.05 ）. Survival analysis showed that high-level expression of HME was significantly correlated with longer survival time （ P 〈 0. 05 ）. Multivariate analysis of prognosis indicated that HME expression and VEGF expression were all independent prognostic factors of gastric carcinoma （P 〈 0. 05 ）. Conclusion High-level expression of HME was significantly associated with hypovascular tumors and better prognosis. HME gene may serve as an effective indicator to predict MVD and prognosis in gastric carcinoma. Expressions of HME and VEGF were both closely related to tumor angiogenesis and prognosis.