肾透明细胞癌中VHL基因改变和趋化因子受体CXCR4的表达及相关性

目的研究肾透明细胞癌（CCRCC）组织中VonHippel-Lindau（VHL）基因改变和趋化因子受体CXCR4的表达及其相关性，探讨VHL基因在CCRCC中的作用。方法分别采用聚合酶链反应-单链构象多态性分析、微卫星法、DNA甲基化特异性PCR和半定量逆转录PCR检测35例CCRCC和20例正常肾组织中VHL基因突变、杂合性缺失（LOH）、异常甲基化及CXCR4mRNA的表达。站杲VHL基因在CCRCC和正常肾组织中的改变率分别为74．29％、5．0％，二者的差异有统计学意义（x^2=24．45，P〈0．01）；VHL基因改变与CCRCC的临床分期、淋巴转移等密切相关（x^2-4．05、5．18，P均〈0．05），而与患者性别、年龄、病理分级、肿瘤大小等均无相关性（P〉0．05）。CXCR4 mRNA在CCRCC中的表达率为77．14％，显著高于正常肾组织的5．0％；CXCR4的表达与CCRCC的病理分级、淋巴转移密切相关（x^2-7．35、4．24，P均〈0．05），而与其他临床病理特征等均无相关性。相关性检验表明CCRCC中VHL基因改变与CXCR4的表达密切相关（x^2-3．89，P〈0．05）。站论VHL基因突变和LOH导致其失活是CCRCC发生的重要分子机制，VHL基因和CXCR4可作为判断CCRCC预后的重要参考指标，并可负向调节CXCR4的表达。

Abnormality of VHL gene and expression of chemokine receptor CXCR4 and their correlation in clear cell renal cell carcinoma

Objective To detect the abnormality of Von Hippcl-Lindau （VHL） gone, expression of chcmokinc receptor CXCR4 and their correlation in clear cell renal cell carcinoma （CCRCC）, and to investigate the role of VHL gene in CCRCC. Methods The polymerase chain reaction single-strand conformational polymorphism analysis, microsatellite method and DNA methylation-specific PCR analysis were respectively used to detect the gene mutation, loss of heterozygosity （LOH） and methylation of VHL gene in 35 CCRCC tissues and 20 normal kidney tissues. The expression of CXCR4 mRNA was examined by semi-quantitivc RT-PCR technique. Results The abnormality of VHL gcnc was 74.29% in CCRCC tissues, which was significantly higher than that （5.0%） in normal tissues （ X^2 = 24.45, P 〈0.01）. The VHL gone inactivations had close correlation with clinical staging and lymphatic metastasis of CCRCC （ X^2 = 4.05 and 5.18, P〈0.01）. No correlation was found between the inactivation and patient age, sexuality, pathological grading and tumor diameter, respectively （P〉0.05）. The expression rate of CXCR4 mRNA in CCRCC was 77.14 %, which was significantly higher than that （5.0 % ） in the normal kidney tissues. The CXCR4 expressions had close correlation with pathological grading and lymphatic metastasis of CCRCC （ X^2 = 7.35 and 4.24, P〈0.05）. However, it had no correlation with other clinical pathological characters. The correlation test showed that there was a significant correlation between the inactivation of VHL gone and expression of CXCR4 （ X^2 = 3.89, P〈0.05）. Oonclusion The VHL gone mutation and LOH resulted in VHL gone inactivation, suggesting that it participated in the molecule mechanism of pathogcncsis and development of CCRCC. VHL gone mutation and CXCR4 could be used as important prognostic indexes. The VHL gone could down-regulate the expression of CXCR4.