Research on the Factor that Determines Susceptibility to Chemotherapy for Musculoskeletal Sarcoma by Genomic/Proteomic Analysis

本研究的目的是利用基因组/蛋白质组学分析方法，阐明原发性肌肉骨骼肉瘤（包括骨肉瘤、尤文氏肉瘤和胃肠道间质瘤（GIST））的预后因素和治疗敏感性相关因素。这项研究的一个特点是通过使用实际的临床肌肉骨骼肉瘤样本，彻底和综合地阐明决定预后和治疗敏感性的基因和蛋白质表达。从各种恶性软组织肉瘤和GISTs的冷冻样品中提取RNA/蛋白质，并使用Affytek U133 GeneChip进行详尽的基因表达分析，并使用荧光二级电泳/质谱进行详尽的蛋白质表达分析。基于基因芯片对恶性软组织肉瘤基因表达的详尽分析，我们发现所谓的恶性纤维组织细胞瘤（MFH）可以分为几个亚型 ...更多信息 这表明根据基因表达模式分别分化成平滑肌肉瘤、脂肪肉瘤等的趋势。我们还通过详尽的蛋白表达分析确定了恶性纤维组织细胞瘤各自组织学类型的特征蛋白，并报道了原肌球蛋白亚型的表达参与了平滑肌肉瘤亚型的亚分类。作为详尽的GIST蛋白表达分析的结果，我们检测到一种蛋白，其表达水平在手术后一年内的早期复发者（预后不良）的手臂和超过两年的无病生存（预后良好）的手臂之间有显着差异。在基因芯片分析中，编码这种蛋白质的mRNA在其表达水平上也表现出类似的变化。这种蛋白质被称为pfetin，并且在使用GIST手术样品的抗pfetin抗体免疫染色和蛋白质印迹中，在良好预后和不良预后组之间也发现了显著差异（p <0.0001）。我们还对原发性肌肉骨骼肉瘤进行了平行的临床和临床病理研究。少

This research is aimed to clarify prognostic factors and factors related to the treatment susceptibility of primary musculoskeletal sarcoma including osteosarcoma, Ewing's sarcoma and gastrointestinal stromal tumor (GIST) using genomic/proteomic analytical methods. A feature of the research was to clarify gene and protein expression that determined the prognosis and susceptibility to treatment exhaustively and integratively by using actual clinical musculoskeletal sarcoma samples. RNA/protein were extracted from frozen samples of various malignant soft tissue sarcomas and GISTs, and exhaustive gene expression analyses were carried out using Affymetrix U133 GeneChip and exhaustive protein expression analyses using fluorescence secondary electrophoresis/mass spectrometry. Based on the results of the exhaustive gene expression analyses of malignant soft tissue sarcomas using GeneChip, we found that so-called malignant fibrous histiocytoma (MFH) could be subclassified into several subtypes … More that suggested a tendency to respectively differentiate into leiomyosarcoma, liposarcoma, etc. depending on the gene expression pattern. We also identified proteins that featured respective histological types of malignant fibrous histiocytoma by exhaustive protein expression analysis, and reported that the expression of tropomyosin subtype was involved in the subclassification of leiomyosarcoma into its subtypes. As a result of exhaustive protein expression analyses of GISTs, we detected a protein that was significantly different in its expression levels between the arm of early relapsers within one year after surgery (poor prognosis), and the arm of disease-free survivals for over two years (good prognosis). The mRNA that encoded this protein demonstrated similar changes in its expression levels also in the GeneChip analysis. This protein is called pfetin, and a significant difference (p<0.0001) was also found between the good prognosis and the poor prognosis arms in the antipfetin antibody immunostaining and Western blotting using GIST surgery samples. We also conducted parallel clinical and clinicopathologic research of primary musculoskeletal sarcoma. Less