【作者】 谷亮；

【导师】 姚阳；

【作者基本信息】 苏州大学 ， 肿瘤学， 2013， 硕士

【摘要】 背景和目的：目前有研究表明MRP4基因参与了多种肿瘤的耐药机制，如胃癌、肺癌及乳癌等。本研究试图探讨MRP4基因在骨肉瘤组织中的表达及其临床意义。方法：收集2005年1月至2011年4月经规范化综合治疗且有完整临床和病理资料的病例50例，其中男性28例，女性22例；Enneking临床分期IIB期41例，III期9例；中位年龄15.5岁（95%CI:15.73-20.93岁）。应用免疫组织化学方法检测骨肉瘤组织及8例瘤旁正常骨组织中MRP4的表达，分析其与骨肉瘤患者临床病理特征及预后的相关性。结果：本试验检测了50例骨肉瘤组织中MRP4的表达。MRP4在骨肉瘤组织细胞浆中的表达率为40%（20/50），明显高于瘤旁正常骨组织的12.5%（1/8），差异有统计学意义（P=0.022）。它的表达水平与骨肉瘤患者的Enneking临床分期、性别、年龄、肿瘤大小、肿瘤部位等无明显的相关性（P>0.05）。41例IIB期骨肉瘤患者中MRP4高水平表达组患者的无病生存时间与低水平表达/不表达组差异不明显（P=0.23），50例患者（41例IIB期和9例III期）中，MRP4高水平表达组患者的总生存时间较低水平表达/不表达组差异亦不显著（P=0.40），它的表达与IIB期患者的总生存时间无明显相关性（P>0.05）。结论：MRP4在骨肉瘤患者组织中的表达高于瘤旁正常骨组织，但MRP4在骨肉瘤组织中不同程度的表达与骨肉瘤患者预后无明显相关，MRP4高表达患者与低表达患者预后无显著差异性。更多还原

【Abstract】 Objective To investigate the expression of MRP4(multidrug resistance associated proteins) in osteosarcoma of extremities, analyze its correlation with clinical and histopathological characteristics, and further discuss its role in the prognosis of osteosarcoma.Methods Immunohistochemical stainning was performed to investigate the expression of MRP4in50cases of osteosarcoma which had complete follow-up data for more than three years.Among this group of patients,there were28males,22females;41stage ⅡB and9stage Ⅲ; with the median age of15.5(95%CI:15.73-20.93).Furthermore, its correlation with patients’ clinical manifestations, histopathological characteristics and its significance in prognosis of osteosarcoma was analyzed basing on the clinical follow-up data.Results This experiment analyzed the expression of MRP4in50cases of osteosarcoma. Compared with that in normal bone cells,MRP4was over-expressed in osteosarcoma cytoplasm (P=0.012). The expression of this marker has no significant difference in the Enneking clinical staging,gender,age,size and location of tumor(P>0.05). Kaplan-Meier analysis showed that in41cases of stage IIB patients,the disease free survival time in MRP4-over-expression patients was similar to that in low-expression/negative-expression patients (P=0.23),and in50patients(41cases of stage ⅡB and9cases of stage Ⅲ),the overall survival time in MRP4-over-expression patients was also similar to that in low-expression/negative-expression patients(P=0.40). In stage ⅡB patients, there was no significant difference between those who showed MRP4-over-expression and those who did not show MRP4-over-expression in the overall survival time (P>0.05).Conclusion MRP4expression in patients with osteosarcoma tissues was significantly higher than the normal bone tissue adjacent to the tumor, but MRP4is not a poor prognostic factor in patients with osteosarcoma,and the MRP4high expression in patients didn’t associated with disease free survival or overall survival.更多还原