摘要
目的:通过微阵列-比较基因组杂交(aCGH)和免疫组织化学技术(IHC),检测RUNX2基因在骨肉瘤组织中的拷贝数变化及蛋白表达情况,探讨RUNX2基因在骨肉瘤的发生、发展和预后中的作用。方法:应用aCGH检测10例新鲜骨肉瘤组织样本RUNX2的基因拷贝数变化;同时,运用免疫组织化学技术检测59例福尔马林固定石蜡包埋(FFPE)骨肉瘤组织中RUNX2蛋白表达水平。结果:10例骨肉瘤样本中发现3例(30%)RUNX2基因扩增;RUNX2蛋白在59例骨肉瘤组织中的阳性表达率为50.8%(30/59)。RUNX2蛋白的表达水平与患者的临床病理特征和生存率无相关性,差异无统计学意义(P>0.05)。Kaplan-Meire单因素生存分析显示pTNM分期、病理诊断、复发、转移和综合治疗对患者的无病生存率有显著影响,性别、pTNM分期、新辅助化疗和疾病转移对患者的总生存率有显著影响,均有统计学意义(P<0.05),但Cox模型多因素生存分析显示这些因素均不能作为生存率独立的预测因素。结论:RUNX2基因扩增、蛋白过表达以及蛋白的表达与骨肉瘤患者的临床特征和预后无相关性提示RUNX2基因扩增及其蛋白的过度表达可能是骨肉瘤发病的早期事件。
This work aimed to investigate the role of the runt-related transcription factor 2 （RUNX2） gene in the pathogenesis, progression, and prognosis of osteosarcoma by detecting the variance of RUNX2 copy number and its protein expression. Methods： Array-based comparative genomic hybridization was used to detect changes in DNA copy number in 10 cases of fresh osteo-sarcoma tissues, focusing on the RUNX2 gene status. The RUNX2 protein expression levels of 59 osteosarcoma cases were assayed by IHC, using formalin-fixed and paraffin-embedded osteosarcoma tissues. Results： RUNX2 gene amplification was observed in 3 of the 10 specimens of osteosarcoma （30%）. The positive rate of RUNX2 protein expression was 50.8% of 59 cases with osteosarcoma （30/59）. RUNX2 protein expression level was not significantly associated with clinicopathological features and survival rate （P〉0.05） in the osteosarcoma patients. The Kaplan-Meire univariate survival analysis showed that the pathologic TNM stage （pTNM）; the diagnosis, re-currence, and metastasis of the cancer; and multidisciplinary therapy had significant effects on the patients＇ disease-free survival. This analysis also showed that sex, pTNM stage, neoadjuvant chemotherapy, and cancer metastasis had significant effects on the patients＇ overall survival （P〈0.05）. However, the COX model multivariate survival analysis showed that these factors could not be used as the in-dependent predictor for survival. Conclusion： RUNX2 gene amplification, elevated protein expression, and lack of association between the clinical characteristics and prognosis of osteosarcoma patients indicate that RUNX2 gene amplification and over-expression of pro-teins may comprise the initial stages of the pathogenesis of osteosarcoma.
出处
《中国肿瘤临床》
CAS
CSCD
北大核心
2013年第7期398-402,共5页
Chinese Journal of Clinical Oncology
基金
国家自然科学基金(编号:30901715)资助~~
关键词
骨肉瘤
RUNX2
微阵列比较基因组杂交
基因扩增
osteosarcoma, runt-related transcription factor 2 RUNX2, aCGH, gene amplification
