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目的:研究胃癌淋巴管生成与淋巴结转移的关系。方法:应用逆转录-聚合酶链反应(RT-PCR)和免疫细胞化学方法检测血管内皮生长因子-C(VEGF-C)和血管内皮生长因子受体-3(VEGFR-3)mRNA及其蛋白在5株胃癌细胞株和3对伴有淋巴结转移的胃癌组织及相应的正常黏膜中的表达。此外,还应用免疫组织化学方法检测86例胃癌标本的淋巴管密度(LVD)和VEGF-C蛋白的表达。结果:VEGF-C mRNA和蛋白高表达于3株胃癌细胞,而VEGFR-3 mRNA和蛋白在上述3个细胞株中均呈弱表达。VEGF-C和VEGFR-3 mRNA均表达于3对伴有淋巴结转移的胃癌和相应的正常黏膜组织中,但在正常组织中的表达水平低于肿瘤组织。VEGF-C蛋白在66.3%(57/86)的病例中呈阳性表达。在伴淋巴结转移的胃癌中,VEGF-C表达较无淋巴结转移者更显著(P<0.001),其表达与淋巴管浸润(P<0.001)和TNM分期(P<0.01)均密切相关,但与病人的年龄和性别、肿瘤大小、位置、组织学类型、浸润深度及远处转移均无明显相关。LVD则与VEGF-C蛋白表达(P<0.001)、淋巴结转移(P<0.01)、淋巴管浸润(P<0.01)、TNM分期(P<0.05)及组织学类型(P<0.05)密切相关,但与病人的年龄和性别、肿瘤大小、位置、浸润深度及远处转移无明显相关。结论:在胃癌中,VEGF-C可能通过VEGFR-3信号通道促进淋巴管生成,从而增加胃癌淋巴结转移率。因此,肿瘤淋巴管生成可能成为治疗胃癌的一个新靶点。
Objective: To study the relationship between lymphangiogenesis and lymph node metastasis in gastric cancer. Methods: The expressions of VEGF-C and VEGFR-3 mRNA and protein were detected by reverse transcription-polymerase chain reaction (RT-PCR) and immunocytochemistry In 5 gastric cancer cell lines and 3 pairs of gastric cancer with lymph node metastasis and the corresponding normal mucosa. In addition, immunohistochemistry was used to detect the expression of lymphatic vessel density (LVD) and VEGF-C protein in 86 gastric cancer specimens. Results: VEGF-C mRNA and protein were highly expressed in three gastric cancer cell lines, while VEGFR-3 mRNA and protein were weakly expressed in the three cell lines. Both VEGF-C and VEGFR-3 mRNA were expressed in 3 pairs of gastric cancer with lymph node metastasis and corresponding normal mucosa, but lower in normal tissues than in tumor tissues. VEGF-C protein was positive in 66.3% (57/86) cases. The expression of VEGF-C in gastric cancer with lymph node metastasis was more significant than that without lymph node metastasis (P <0.001). The expression of VEGF-C was closely related to lymphatic invasion (P <0.001) and TNM stage Patient’s age and gender, tumor size, location, histological type, depth of invasion and distant metastasis were not significantly correlated. LVD was closely related to VEGF-C protein expression (P <0.001), lymph node metastasis (P <0.01), lymphatic invasion (P <0.01), TNM stage (P <0.05) and histological type (P < However, there was no significant correlation between the patient’s age and sex, tumor size, location, depth of invasion and distant metastasis. Conclusion: In gastric cancer, VEGF-C may promote lymphangiogenesis via VEGFR-3 signaling pathway and increase the rate of lymph node metastasis in gastric cancer. Therefore, tumor lymphangiogenesis may become a new target for the treatment of gastric cancer.