骨肉瘤细胞和外周血淋巴细胞ERCC2与ERCC4基因表达及其临床意义

目的:检测ERCC2与ERCC4基因在骨肉瘤细胞和外周血淋巴细胞中的表达与化疗效果之间的关系.方法:选取26例骨肉瘤患者,取其化疗前切开活检标本的肿瘤细胞与外周血淋巴细胞.对化疗后肿瘤切除标本进行肿瘤坏死率检查.应用荧光实时定量PCR相对定量方法检测肿瘤细胞与外周血淋巴细胞中ERCC2 与ERCC4 的mRNA表达水平,分析其表达水平与化疗后肿瘤坏死率之间的关系,及其表达水平和患者性别、年龄、肿瘤体积、分期、碱性磷酸酶、乳酸脱氢酶等各临床因素之间的关系.并分别对ERCC2 与ERCC4 在肿瘤细胞与外周血淋巴细胞中mRNA表达水平进行相关性分析.结果:(1)肿瘤坏死率较高组的骨肉瘤细胞中ERCC4 mRNA相对定量(6.29±1.20)要高于肿瘤坏死率较低组(5.14±1.16),P=0.023;肿瘤坏死率较高组中外周血淋巴细胞ERCC4 mRNA相对定量(5.59±1.15)要高于肿瘤坏死率较低组(4.52±1.20),P=0.032;ERCC4 mRNA在骨肉瘤细胞和淋巴细胞中的表达具有相关性,r=0.768,P＜0.01;(2)肿瘤坏死率较高组的骨肉瘤细胞中ERCC2 mRNA相对定量(3.49±1.14)要高于肿瘤坏死率较低组(2.33±1.31),P=0.029;(3)年龄较低组的骨肉瘤细胞中ERCC4 mRNA相对定量(6.42±1.26)要高于年龄较大组(5.35±1.07),P=0.046;碱性磷酸酶正常组的骨肉瘤细胞中ERCC2 mRNA相对定量(3.85±1.08)高于碱性磷酸酶升高组(2.55±1.25),P=0.013.结论:检测骨肉瘤细胞中ERCC4和ERCC2的mRNA表达水平以及外周血淋巴细胞中ERCC4的 mRNA表达水平,对预测骨肉瘤的化疗效果及其预后具有一定的指导意义.

Expressions of ERCC2 and ERCC4 genes in osteosarcoma and peripheral blood lymphocytes and their clinical significance

OBJECTIVE: To detect the expressions of ERCC2 and ERCC4 genes in osteosarcoma (OS) and peripheral blood lymphocyte (PBL), and their relationship with the prognosis to provide potential markers for evaluating the chemotherapeutic effect and prognosis of OS. METHODS: Between Jan. 2006 and Nov. 2006, 26 OS patients were chosen for this study. A small quantity of specimens were obtained in the open biopsy before chemotherapy, as well as 5 mL venous blood to separate PBLs. All of the patients received chemotherapy preoperatively and then operation. After the operation, the resected tumor specimens were examined completely for tumor necrosis rates which were related to chemotherapy. The tumor necrosis rates were classified into two groups, high tumor necrosis (TN) group and low TN group. The expressions of ERCC2 mRNA and ERCC4 mRNA of OS cells in open biopsy specimens were analysed by real time PCR, and so were those of the PBLs from venous blood. The correlations of mRNA expression level of the two genes both in OS cells and in PBLs with different tumor necrosis groups were analysed,respectively. The correlations of ERCC2 mRNA in OS and PBLs were analyzed, and so were those of ERCC4 mRNA level. And their associations with clinical features, including sex, age, tumor volume, tumor stages, alkaline phosphatase (AKP) and lactate dehydro-genase (LDH) were analyzed , respectively. All of the data were processed statistically with SPSS software. RESULTS: The expression levels of ERCC4 mRNA in OS cells of high TN group (6.29+/-1.20) were significantly higher compared to those of the low TN group (5.14+/-1.16), P=0.023. Also the expression levels of ERCC4 mRNA in PBLs of high TN group (5.59+/-1.15) were significantly higher compared to those of the low TN group (4.52+/-1.20), P=0.032. And there was a positive correlation between ERCC4 mRNA levels in OS and in PBLs (r=0.768, P<0.01). ERCC2 mRNA only in OS cells of high TN group (3.49+/-1.14) were significantly higher compared to those of the low TN group (2.33+/-1.31), P=0.029. ERC4 expression in OS was significantly associated with age and ERCC2 expression in OS was significantly associated with AKP level, respectively. CONCLUSION: The expressions of ERCC4 mRNA in OS cells or PBLs and ERCC2 mRNA were correlated with chemotherapeutic effect of osteosarcoma. The detection of the genes above may be useful for evaluating prognosis.