胃癌中CXCR4和CD133的表达及其对淋巴转移的影响

Expressions of CXCR4 and CD133 in stomach cancer and their roles in lymphatic metastasis

目的:探讨CXCR4和CD133在胃癌原发灶中的表达及其对淋巴转移的影响。方法:对50例原发性胃癌原发灶和癌旁胃黏膜组织行免疫组化染色法定位检测CXCR4和CD133蛋白;选用半定量RT-PCR及Western blot法测定CXCR4和CD133 mRNA与蛋白表达量,分析两者的相关性及其与淋巴管浸润和淋巴结转移的关系。结果:CXCR4和CD133分子均定位于肿瘤细胞膜表面,极少数CXCR4位于细胞核内。胃癌组织中CXCR4和CD133表达阳性率及mRNA和蛋白的表达量均明显高于癌旁胃黏膜组织(均P<0.05);CXCR4和CD133 mRNA相对灰度值在淋巴结转移组高于无淋巴结转移组(P=0.011,P=0.038);N1组CXCR4蛋白相对灰度值明显高于N0组(P=0.023),而低于N2+N3组(P=0.008),N1组和N2+N3组CD133蛋白灰度值明显高于N0组(P=0.04,P=0.01),但N1组与N2+N3组之间无明显差异;淋巴管浸润组中的CXCR4和CD133蛋白相对灰度值均高于淋巴管无浸润组(P<0.05);在淋巴转移患者中,CXCR4和CD133蛋白相对灰度值分别与转移淋巴结数(r=0.480,r=0.426)及转移性淋巴结比率(r=0.502,r=0.489)呈正相关。结论:CXCR4和CD133在胃癌原发灶中高表达,两者呈正相关,其联合表达与转移淋巴结比率和转移淋巴结数呈正相关,推测胃癌CD133阳性细胞亚群可能在CXCR4介导下更易导致淋巴管浸润和淋巴结转移。

Objective： To determine the expressions of CXCR4 and CD 133 in the primary lesions of gastric cancer, and their influences on lymphatic metastasis.Methods： The primary tumor tissues and their adjacent normal mucosal tissues were taken from S0 gastric cancer patients. In these tissues, the location of CXCR4 and CD133 expression was detected by immunohistochemical staining, the gene and protein expression levels of CXCR4 and CD 133 were determined by semi-quantitative RT-PCR and Western blot, respectively： and the correlations between CXCR4 and CD133 and their relations with lymphatic vessel invasion and lymph node metastasis were analyzed. Results： The CXCR4 and CD 133 molecules were both expressed on the membranes of tumor cells and very small amount of CXCR4 was found in the nucleus.The positive expression rates as well as the gene and protein expression levels of CXCR4 and CD133 in gastric cancer tissues were all significantly higher than in those of the normal mucosal tissues （all P〈0.05）. The relative gray scale values of both CXCR4 and CD133 mRNA were significantly higher in the tumor tissues of the group with lymph node metastases than in those without lymph node involvement （P=0.011 and P=0.038）. The relative gray scale value of the CXCR4 protein in the tumor tissues of the group with N1 lymph node involvement was significantly higher than in those without lymph node metastasis （P=0.023）, but was lower than in those with Nz＋N3 lymph nodes involvement （P=0.008）. The relative gray scale value of the CD 133 protein in the tumor tissues of the group with N1 or N2＋N3 lymph node involvement was significantly higher than in those without lymph node involvement （P=0.04 and P=0.01）, but there was no significant difference between the N1 and N2＋N3 groups. The relative gray scale values of CXCR4 and CD133 protein in the tumor tissues of the group with lymphatic vessel invasion were significantly higher than in those without lymphatic vessel invasion （P〈0.05）. Of the patients with lymph nodes metastases, the relative gray scale values of both CXCR4 and CD133 protein were positively correlated with the number of lymph nodes involved （r=0.480, r=0.426） and the ratio of metastatic lymph nodes （r=0.502, r=-0.489）. Conclusion： CXCR4 and CD 133 present high expression and are positively correlated in the primary lesion of stomach cancer, and the expression of both of these proteins is associated with the metastatic lymph node ratio and number. It is speculated that under the mediation of CXCR4, lymphatic vessel invasion and metastasis of CD 133 postitive tumor cells is more easily induced.