Center of Orthopedic Surgery, The Orthopedics Oncology Institute of Chinese PLA, The Affiliated Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
Mol Carcinog. 2014 Feb;53(2):138-44. doi: 10.1002/mc.21957. Epub 2012 Sep 4.
Osteosarcoma (OSA) is the most common primary malignancy of bone. Molecular mechanism underlying OSA remains to be fully elucidated. It is critical to identify reliable diagnostic and prognostic markers for OSA at the molecular levels. This study is designed to investigate possible molecular mechanisms behind OSA development and to identify novel prognostic markers related to OSA survival. We conduct a comprehensive proteomic profiling analysis of human OSA cell lines with differential metastatic potential. Through comprehensive combinatorial analyses of the proteomic data and the previously obtained cDNA microarray results, we identify 37 candidate proteins which are differentially expressed in OSA sublines. Among them, ALDOA and SULT1A3 are selected for further investigation. The expressions of protein are confirmed by Western blotting analysis. We further analyze the expression levels of ALDOA and SULT1A3 from 40 clinical cases of OSA. The results demonstrate that the expression of ALDOA and/or SULT1A3 is significantly higher in patients with worse survival time than patients with better survival time. Five-year survival analysis shows there is a statistically significant difference between two patient populations. The data strongly suggest that ALDOA and/or SULT1A3 expression level in biopsy samples may predict the clinical outcomes of OSA patients. Furthermore, the biological functions of ALDOA and SULT1A3 may be implicated in OSA development and/or progression.
骨肉瘤（OSA）是最常见的原发性骨恶性肿瘤。OSA 的分子机制仍有待充分阐明。在分子水平上，识别可靠的 OSA 诊断和预后标志物至关重要。本研究旨在探讨 OSA 发生的可能分子机制，并鉴定与 OSA 生存相关的新型预后标志物。我们对具有不同转移潜能的人骨肉瘤细胞系进行了全面的蛋白质组谱分析。通过对蛋白质组数据和先前获得的 cDNA 微阵列结果进行综合组合分析，我们确定了 37 种在 OSA 亚系中差异表达的候选蛋白。其中，ALDOA 和 SULT1A3 被选中进行进一步研究。通过 Western blot 分析验证了蛋白质的表达。我们进一步分析了 40 例 OSA 临床病例中 ALDOA 和 SULT1A3 的表达水平。结果表明，ALDOA 和/或 SULT1A3 的表达在生存时间较差的患者中明显高于生存时间较好的患者。5 年生存分析显示，两组患者之间存在统计学差异。数据强烈表明，活检样本中 ALDOA 和/或 SULT1A3 的表达水平可能预测 OSA 患者的临床结局。此外，ALDOA 和 SULT1A3 的生物学功能可能与 OSA 的发展和/或进展有关。
