成骨细胞相关基因在软骨肉瘤中的表达

摘要

目的通过对软骨肉瘤细胞中成骨细胞相关基因的表达进行分析，探讨软骨肉瘤中细胞分化的分子表型。方法采用RT-PCR和印记方法半定量测定32例软骨肉瘤患者骨钙素（OC）、碱性磷酸酶(AP)、骨结合蛋白(ON) 和Cbfa 1的表达，分析其与组织学分级和预后的关系。结果病理学分级与OC、AP或Cbfa 1表达有明显相关性；成骨细胞相关基因在Ⅲ级软骨肉瘤的表达最为多见。骨钙素mRNA表达的检测，在12例Ⅲ级患者有9例可测到（75％），在20例Ⅰ～Ⅱ级患者中有4例可测到（20％）（P=0.008）。在32例患者中，21个可测到AP mRNA，其中12例Ⅲ级患者中有11例（92％）、20例Ⅰ～Ⅱ级患者中有10例（50％）可测到AP的表达（P=0.018）。OC或AP表达常与无病生存率下降相联系(OC:P=0.016; AP:P=0.018)。Cbfa1 mRNA只在4例Ⅲ级软骨肉瘤中测到。所有软骨肉瘤中均可测到ON，表明其表达与病理分级及无病生存率无相关性。结论绝大多数Ⅲ级软骨肉瘤中可测到OC的表达，而在Ⅰ～Ⅱ级软骨肉瘤中只有少数表达，并且OC的表达常与预后差相关联；AP mRNA阳性率在Ⅰ～Ⅱ级和Ⅲ级中有明显的差别，AP的表达也和无病生存率下降呈正相关；在软骨肉瘤中OC或AP的表达可做为独立的预后指标；Cbfa 1在分级高的软骨肉瘤中较常表达，表现出与OC有相同的特性。%Objective　To analyze the expression of osteoblast-associated genes in chondrosarcomas and to identify phenotypes of tumor cell differentiation.　Methods　Expression of osteocalcin (OC),alkaline phosphatase (AP),osteonectin (ON)　and core binding factor A1 (Cbfa1) was analyzed semi-quantitatively by RT-PCR and blotting and　was correlated with histologic grade and prognosis in 32 chondrosarcoma patients.　Results　There were statistically significant relations between the pathologic grade and the presence of OC, AP or Cbfa1 transcripts. These osteoblast-associated genes were more often expressed in grade Ⅲ chondrosarcomas. Osteocalcin mRNA expression was detected in 9 of 12 (75%) grade Ⅲ chondrosarcomas and 4 of 20 (20%) grade Ⅰ-Ⅱ chondrosarcomas (P=0.008). AP mRNA was found in 21 of 32 chondrosarcomas,including 11 of 12 (92%) grade Ⅲ and 10 of 20 (50%) grade Ⅰ-Ⅱ chondrosarcomas (P=0.018).OC or AP transcript was associated with decreased disease free survival (P=0.016 for OC,and P=0.018 for AP, Log-rank test).Cbfa1 mRNA was only detected in 4 grade Ⅲ chondrosarcomas. ON was detected in all chondrosarcoma samples. No correlation was observed between ON transcript and pathological grade or disease free survival.　Conclusions　OC transcript may be detected in the majority of high grade, but in a few grade Ⅰ-Ⅱ chondrosarcomas, and is associated with poor prognosis in patients with chondrosarcoma. The difference in AP mRNA positivity between grade　Ⅰ-Ⅱ and grade Ⅲ group is significant. AP expression is also related to decreased disease free survival. OC or AP expression in chondrosarcoma might be of independent prognostic value. Cbfa1 appears to have similar features with OC in that it is expressed more frequently in high grade chondrosarcomas.