背景与目的:浸润与转移是恶性肿瘤的重要生物学特性,经血管和淋巴管播散是肿瘤转移的两条重要途径.淋巴管是实体肿瘤转移的最早通路之一,但与肿瘤血管相比,对肿瘤淋巴管的研究甚少.近年,随着血管内皮生长因子-C(vascular endothelial growth factor-C,VEGF-C)、血管内皮生长因子-D(vascularendothelial growth factor-D,VEGF-D)以及多种淋巴管内皮特异性标志物,如淋巴管内皮透明质酸受体-1(lymphatic vessel endothelial hyaluronan receptor-1,LYVE-1)、血管内皮生长因子受体-3(vascularendothelial growth factor receptor-3,VEGFR-3)、肾小球足突膜蛋白(glomerular podocyte membrancemucoprotein,podoplanin)和同源异型盒转录因子(the homeobox transcription factor,Prox-1)等先后被鉴定,淋巴管生成己成为肿瘤转移研究领域的热点之一.本文探讨前蛋白转换酶(proprotein convertase,PC)5、7,VEGF-C、-D及其受体VEGFR-3在非小细胞肺癌(non-small cell lung cancer,NSCLC)中的表达规律及其在NSCLC发生发展、淋巴转移及预后中的意义.方法:以20例经病理确诊的NSCLC组织、肿瘤周边组织为实验组,以9例肺良性病变组织为对照组,采用实时荧光定量RT-PCR方法对上述组织中PC5、PC7、VEGF-C、VEGF-D及VEGFR-3 mRNA的表达进行定量分析.结果:①NSCLC组织中PC5、PC7、VEGF-C、VEGF-D及VEGFR-3 mRNA的表达量均显著高于肿瘤周边组织及肺良性病变组织(P<0.05).②PC5、PC7、VEGF-C、VEGF-D及VEGFR-3 mRNA的表达量与NSCLC患者的性别、年龄、肿瘤的大小、组织学类型、分化程度无关,但与肿瘤的淋巴结转移(P=0.000,P=0.000,P=0.012,P=0.000,P=0.004)、PTNM分期(P=0.011,P=0.012,P=0.013,P=0.011,P=0.028)显著相关.③PC5与VEGF-C(=0.461,P=0.041)、VEGF-D(r=0.793,P=0.000)及VEGFR-3(P=0.498,P=0.026)mRNA表达存在相关性;PC7与VEGF-C(r=0.450,P=0.047)、VEGF-D(r=0.699,P=0.001)及VEGFR-3(r=0.616,P=0.004)mRNA表达存在相关性.并且,VEGF-C与VEGF-D(r=0.532,P=0.016)、VEGF-C与VEGFR-3(r=0.607,P=0.001)及VEGF-D与VEGFR-3 mRNA的表达(r=0.451,P=0.048)均存在相关性.结论:淋巴管生成因子VEGF-C、VEGF-D、VEGFR-3及调节其成熟的转换酶PC5、PC7 mRNA在NSCLC中表达显著增高,并且通过VEGF-C,VEGF-D/VEGFR-3信号通路诱导淋巴管内皮细胞新生和淋巴管生成,促进淋巴结转移和肿瘤生长:VEGF-C、VEGF-D及其受体VEGFR-3可能成为检测NSCLC淋巴转移和评估预后的重要分子指标;实时荧光定量RT-PCR技术是一种简单客观敏感的检测肿瘤微转移的方法,有助于早期肺癌淋巴微转移的检测.%Background and purpose: Infiltration and metastasis are characteristic of the biological behavior of cancer. Blood circulation and lymphatic spread are two important ways for neoplasm metastasis. The lymphatic vessel is one of the earliest routes for solid neoplasm metastasis. However, compared to tumor blood vessels, there were only a few studies on the research for lymphatic vessel spread. In recent years, with the identification of vascular endothelial growth factor-C (VEGF-C), VEGF-D and lymphatic endothelial markers including lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), vascular endothelial growth factor receptor-3 (VEGFR-3), glomerular podocyte membrance mucoprotein (podoplanin) and the homeobox transcription factor (Prox-1), lymphangiogenesis has become one of the important areas in the study of tumor metastasis. This paper was to study the expression of proprotein convertase (PC)5, PC7, VEGF-C, VEGF-D and their receptor VEGFR-3 in patients with non-small cell lung cancer (NSCLC) and their clinico-pathoiogical value. Methods: Twenty specimens of the NSCLC, peritumoral tissues as experimental group and nine pulmonary benign diseases as control group were studied. The expression of PC5, PC7, VEGF-C, VEGF-D and VEGFR-3 mRNA in specimens of those tissues were studied by real-time quantitative reverse transcriptase polymerase chain reaction (real-time quantitative RT-PCR). Results: ①The expressions of PC5, PC7, VEGF-C, VEGF-D, VEGFR-3 mRNA in specimens of NSCLC were significantly higher than those of the peritumoral and pulmonary benign diseases tissues (P展开▼
