Granzyme B在原发及淋巴转移性胃癌细胞中的差异表达及其与肿瘤血管生成的关系

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目的:探讨胃癌细胞Granzyme B(GrB)表达在肿瘤血管生成和淋巴转移中的作用.方法:以细胞毒T淋巴细胞为内对照,采用免疫组织化学染色S-P法检测35例胃癌及其中23例淋巴转移癌细胞GrB蛋白的表达;同法检测35例胃癌血管内皮生长因子(VEGF)的表达及CD34标记的微血管密度(MVD).结果:GrB的表达在无淋巴转移的胃癌高于有淋巴转移者,但无显著性差异,但淋巴转移灶的胃癌细胞GrB阳性率较相应的原发肿瘤显著增高(P=0.038);胃癌GrB与VEGF表达的同步率达57.1%,两者表达水平无明显相关性,而GrB表达水平与胃癌MVD呈显著负相关(r=-0.421,P=0.012);GrB阳性胃癌无论其VEGF表达水平如何,其MVD无显著差异; VEGF阳性胃癌MVD与GrB的表达状态明显相关,GrB阳性者MVD显著下降(P=0.023),在VEGF阴性胃癌中也有类似结果;GrB+&VEGF-表型胃癌MVD最低,VEGF+&GrB-表型胃癌MVD最高,两者有显著性的差异(P= 0.013).结论:胃癌细胞GrB表达可能有助于抑制肿瘤血管生成,但也可能有助于淋巴转移胃癌细胞的存活. Objective: To investigate the role of Granzyme B (GrB) expression in tumor angiogenesis and lymphatic metastasis. Methods: Cytotoxic T lymphocytes were used as control. The expression of GrB protein in 35 cases of gastric carcinoma and 23 cases of lymphatic metastasis cells was detected by immunohistochemical SP method. The expression of GrB protein in 35 cases of gastric carcinoma with vascular endothelial growth factor (VEGF) Expression and CD34 labeled microvessel density (MVD). Results: The expression of GrB in gastric cancer with lymphatic metastasis was higher than those with lymphatic metastasis, but there was no significant difference. However, the positive rate of GrB in gastric cancer with lymphatic metastasis was significantly higher than that of the corresponding primary tumor (P = 0.038). The synchronous rate of GrB and VEGF expression in gastric cancer was 57.1%, but there was no significant correlation between the expression of GrB and VEGF. However, the expression of GrB was negatively correlated with MVD in gastric cancer (r = -0.421, P = 0.012) There was no significant difference in MVD between positive gastric cancer and normal gastric cancer, MVD was positively correlated with GrB in VEGF positive gastric cancer, MVD was significantly decreased in GrB positive patients (P = 0.023), and similar results were found in VEGF negative gastric cancer. The MVD of GrB + & VEGF-phenotype gastric cancer was the lowest, and MVD of VEGF + & GrB-phenotype gastric cancer was the highest with significant difference (P = 0.013). CONCLUSIONS: GrB expression in gastric cancer cells may help to inhibit tumor angiogenesis, but may also contribute to the survival of gastric cancer cells with lymphatic metastasis.
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