摘要
目的结、直肠癌发展过程中出现的淋巴结转移被认为与其预后关系密切。淋巴生成因子及淋巴管密度被认为与肿瘤的淋巴结转移有关。VEGF家族中,VEGF-C和VEGF-D具有促进淋巴管生成的作用,而VEGF-D被认为是VEGF家族中唯一的一个专一的淋巴生长促进因子。Podoplanin首先在肾足细胞上被发现,后来发现它主要存在于成人的肺脏,淋巴内皮表面亦有表达,而且Podoplanin只存在于淋巴内皮,血管内皮并无表达。另外,Podolplanin和VEGFR-3共存,这证明Podoplanin是淋巴管的标记物。TEM(tumor endothelial marker)是新发现的肿瘤特异性的内皮标记物,一般认为和肿瘤血管生成有关。TEM-8是个例外,它被发现与肿瘤的淋巴结转移有相关性。
本试验的目的是检测结直肠癌组织中VEGF-D,TEM-8,Podoplanin的含量,并分析其与局部淋巴结转移的相关性。
方法用实时半定量PCR方法分析30例结、直肠癌标本中TEM-8,Podoplanin,VEGF-D的表达,并结合病理学分期,淋巴结转移等肿瘤特点进行分析
结果VEGF-D,TEM-8,Podoplani水平在肿瘤组织中均较癌旁组织中升高(VEGF-D在肿瘤组织中含量为0.0055±0.0036,癌旁组织中为0.0015±0.0015,P＜0.05,podoplanin在肿瘤组织中含量为0.0136±0.0106,癌旁组织中为0.0014±0.0018,P＜0.05,TEM-8在肿瘤组织中含量为0.0006±0.0004,癌旁组织中为0.0043±0.0035,P＜0.05)。Podoplanin的含量在Dukes B(0.0074±0.0126),DukesC(0.0171±0.0159)样本之间显示显著性差异(P＜0.05)。在有淋巴结转移(0.0247±0.0218)和无淋巴结转移(0.00681±0.0108)的样本之间亦显示有明显差异(P＜0.05)。VEGF-D的含量在Dukes B(0.00486±0.00186),Dukes C(0.00621±0.00269)样本中未显示明显差异(P＞0.05)。在有淋巴结转移(0.00847±0.00218)和无淋巴结转移(0.00481±0.00108)的样本之间则显示有明显差异(P＜0.05)。TEM-8在Dukes B,Dukes C样本中的含量分别为0.0028±0.0141,0.00375±0.0162,有显著性差异(P＜0.05)。在有淋巴结转移(0.00415±0.0137)和无淋巴结转移(0.00213±0.00584)的样本之间亦显示有明显差异(P＜0.05)。
结论TEM-8,Podoplanin,VEGF-D均可作为结、直肠癌的标记物,并可反映淋巴结转移状况,TEM-8更可作为肿瘤特异性标记物,在结、直肠癌的诊断,预后判断,治疗中可望发挥重要作用。
Objectives Lymphatic spread of colorectal cancer cells to regional lymph nodes is one of the early events in metastatic cancers and often is associated with distant metastatic spread and a poor prognosis.In this experiment,the expression levels of lymphatic endothelial markers—VEGF-D,podoplanin,and a newly described tumor marker,TEM-8 were assessed half-quantified by using a real-time PCR(RT-PCR) technique,to evaluate the prognostic value of the three markers in colorectal cancer.
methods Tumor tissue and adjacent normal mucosa were obtained from 30 colorectal cancer patients immediately after surgical resection.Levels of VEGF-D, podoplanin and TEM-8 were examined for each sample using real-time RT-PCR.
Results VEGF-D,podoplanin,and TEM-8 levels were significantly higher in tumor tissues than that in normal mucosa(VEGF-D level detected in tumor tissue was 0.0055±0.0036,and in normal mucosa,0.0015±0.0015,P＜0.05,podoplanin levels in tumor tissues and normal mucosa were 0.0136±0.0106,and 0.0014±0.0018, respectively,P＜0.05,and for TEM-8 levels,0.0006±0.0004,in tumor tissues,0.0043±0.0035,in normal mucosa,P＜0.05).In the cases with regional lymphnode metastasis,VEGF-D levels were significantly higher than those without(0.00847±0.00218,and 0.00481±0.00108,respectively,P＜0.05),but no correlation was found between VEGF-D level and tumor stage(in Dukes B group,VEGF-D level was 0.00486±0.00186,in Dukes C,0.00621±0.00269,P＞0.05).While TEM-8(Dukes B,0.0028±0.0141,Dukes C,0.00375±0.0162,P＜0.05,lymphnode positive, 0.00415±0.0137,lymphnode negative,0.00213±0.00584,P＜0.05) and podoplanin (Dukes B,0.0074±0.0126,Dukes C,0.0171±0.0159,P＜0.05,lymphnode positive, 0.0247±0.0218,lymphnode negative,0.00681±0.0108,P＜0.05) levels was correlated with both regional node metastasis and tumor stage.
Conclusion VEGF-D,Podoplanin and TEM-8 could act as tumor markers for colorectal cancer,and were correlated with regional lymphnode metastasis.TEM-8 was proved to be an tumor spicific marker,may play an important role in the diagnosis,prognostic prediction,and treatment of colorectal cancer.
引文
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