Wang Guoxiang, Zhang Zhengyao, Yang Maoguang, Xu Bo, Gao Qi, Yang Xiaoyu
Department of Orthopedics, The Second Hospital of Jilin University, ZiQiang Street,130041 ChangChun, China; Department of Orthopedics, The First Hospital of Jilin University, XinMin Street,130041 ChangChun, China.
School of Life Science and Medicine, Dalian University of Technology, DaGong Road, 124221 PanJin, China.
J Bone Oncol. 2016 May 12;5(4):147-152. doi: 10.1016/j.jbo.2016.05.002. eCollection 2016 Nov.
Osteosarcoma (OS) is the most common primary malignant tumor of bone and the third most common cancer in childhood and adolescence. However, controversy concerning the ideal combination of chemotherapy agents ensued throughout the last quarter of the 20th century because of conflicting and often nonrandomized data. Collaborative efforts to increase understanding of the biology of osteosarcoma and the use of preclinical models to test novel protein targets will be critical to identify the path toward improving outcomes for patients. We attempted to identify potential protein markers or therapy targets of osteosarcoma and give a glance at tumorigenesis of osteosarcoma. A sensitive and accurate method was employed in comparative proteomic analysis between benign tumor and osteosarcoma. Tumor tissues obtained by open biopsy before induction chemotherapy were investigated With 2D DIGE and MALDI-TOF/TOF MS, 22 differentially expressed proteins were identified after database searching, including 8 up-regulated and 14 down-regulated proteins. We also validated the expression levels of interesting proteins(have higher Ratios(tumor/normal)) by Western blotting assay. Annotating by bioinformatic tools, we found structural and signal transduction associated proteins were in large percentage among altered level proteins. In particular, some low abundant proteins involving translation and transcription, such as EEF2(Elongation Factor 2), LUM Lumican 23 kDa Protein) and GTF2A2(Transcription Initiation Factor Iia Gamma Chain.), were firstly reported by our study comparing to previous observations. Our findings suggest that these differential proteins may be potential biomarkers for diagnosis or molecules for understanding of osteosarcoma tumorigenesis, coming with biologic, preclinical, and clinical trial efforts being described to improve outcomes for patients.
骨肉瘤（OS）是最常见的原发性骨恶性肿瘤，也是儿童和青少年中第三常见的癌症。然而，由于数据相互矛盾且往往未经随机化处理，在20世纪的最后25年里，关于化疗药物理想组合的争议一直存在。加强对骨肉瘤生物学的理解以及利用临床前模型测试新的蛋白质靶点的合作努力，对于确定改善患者预后的途径至关重要。我们试图识别骨肉瘤的潜在蛋白质标志物或治疗靶点，并简要了解骨肉瘤的肿瘤发生过程。在良性肿瘤和骨肉瘤之间的比较蛋白质组分析中采用了一种灵敏且准确的方法。对诱导化疗前通过开放活检获得的肿瘤组织进行二维差异凝胶电泳（2D DIGE）和基质辅助激光解吸电离飞行时间串联质谱（MALDI-TOF/TOF MS）分析，数据库搜索后鉴定出22种差异表达蛋白，其中8种上调，14种下调。我们还通过蛋白质印迹分析验证了感兴趣蛋白质（肿瘤/正常比值较高）的表达水平。通过生物信息学工具进行注释，我们发现结构和信号转导相关蛋白在水平改变的蛋白质中占很大比例。特别是，一些涉及翻译和转录的低丰度蛋白，如延伸因子2（EEF2）、亮蛋白聚糖23 kDa蛋白（LUM）和转录起始因子IIaγ链（GTF2A2），与以往观察结果相比，首次在我们的研究中被报道。我们的研究结果表明，这些差异蛋白可能是骨肉瘤诊断的潜在生物标志物或理解骨肉瘤肿瘤发生的分子，同时还描述了为改善患者预后而进行的生物学、临床前和临床试验努力。
