骨肉瘤DNA损伤修复相关基因表达与预后的关系

目的研究DNA损伤修复基因MPG、APE1、XRCC1和MGMT在人体骨肉瘤中的表达特点及其与患者预后的关系,为判估骨肉瘤对化疗的反应性及其预后提供有价值的指标.方法应用免疫组化方法检测60例骨肉瘤组织和3株骨肉瘤细胞中MPG、APE1、XRCC1和MGMT的表达,按染色强度将其分为低表达组和高表达组.统计分析它们与临床病理及患者预后的关系.结果3株骨肉瘤细胞中APE1和XRCC1呈强阳性,MPG和MGMT呈弱阳性.60例骨肉瘤中MPG、APE1、XRCC1和MGMT高表达分别为40例(65%)、43例(72%)、23例(38%)和32例(53%).APE1表达和患者年龄,Price's分级和WHO分型有显著性差异(P＜0.05),MPG表达和WHO分型有显著性差异(P＜0.05).Spearman秩相关检验显示上述4项指标之间密切相关.单因素相关分析显示APE1和MPG表达与患者预后有显著性差异(P＜0.05),COX比例风险模型显示MPG表达与患者预后有关(P＜0.01).结论DNA损伤修复基因MPG、APE1、XRCC1和MGMT的共同表达是骨肉瘤的特点,APE1和MPG表达对于判估骨肉瘤患者的预后可能更有意义.

Prognostic significance of DNA damage and repair gene expression in human osteosarcoma

Objective To detect the expression of DNA repair related proteins, including MPG, APE1, XRCC1 and MGMT in osteosarcoma and their relationship with the prognosis to provide potential markers for evaluating the chemotherapeutic reaction and prognosis of osteosarcoma. Methods The expression of MPG, APE1, XRCC1 and MGMT were determined by immunohistochemical staining in 60 specimens and 3 cell lines (HOS, SAO-2, U-2OS) of human osteosarcoma. High expression group and low expression group were divided according to the staining intensity, and their association with clinicopathological data as well as prognosis was analyzed statistically with SAS software. Results The high expressions of MPG, APE1, XRCC1 and MGMT were found in 40 cases (67%), 43 cases (72%), 23 cases (38%) and 32 cases (53%) respectively. APE1 expression was significantly associated with age, Price's grading and WHO histological classification (P<0.05), while MPG expression was significantly associated with WHO histological classification only (P<0.05). MPG, APE1, XRCC1 and MGMT expressions were remarkably related with each other by spearman relation test (P<0.05). APE1 and MPG expressions were statistically related with prognosis by single factor regression analysis (P<0.05). Moreover, only MPG expression was related with prognosis by COX proportion hazard multivariate analysis (P<0.01). Conclusion The coexpression or related expression of DNA repair proteins MPG, APE1, XRCC1 and MGMT is the important expression pattern in human osteosarcoma. Among them, the MPG and APE1 proteins may be more valuable to therapeutic implications for osteosarcoma.