Chen Shuxin, Li Chunquan, Wu Bingli, Zhang Chunlong, Liu Cheng, Lin Xiaoxu, Wu Xiangqiao, Sun Lingling, Liu Chunpeng, Chen Bo, Zhong Zhigang, Xu Liyan, Li Enmin
Key Laboratory of Molecular Biology in High Cancer Incidence Coastal Chaoshan Area of Guangdong Higher Education Institutes, Medical College of Shantou University, Shantou 515041, P.R. China.
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, P.R. China.
Int J Oncol. 2014 Sep;45(3):1133-42. doi: 10.3892/ijo.2014.2501. Epub 2014 Jun 18.
Giant cell tumor (GCT) of the bone is a benign but locally aggressive bone neoplasm with a strong tendency to develop local recurrent and metastatic disease. Thus, it provides a useful model system for the identification of biological mechanisms involved in bone tumor progression and metastasis. This study profiled 24 cases of recurrent versus primary bone GCT tissues using QuantiGene 2.0 Multiplex Arrays that included Human p53 80-Plex Panels and Human Stem Cell 80-Plex Panels. A total of 32 differentially expressed genes were identified, including the 20 most upregulated genes and the 12 most downregulated genes in recurrent GCT. The genes identified are related to cell growth, adhesion, apoptosis, signal transduction and bone formation. Furthermore, iSubpathwayMiner analyses were performed to identify significant biological pathway regions (subpathway) associated with this disease. The pathway analysis identified 11 statistically significant enriched subpathways, including pathways in cancer, p53 signaling pathway, osteoclast differentiation pathway and Wnt signaling pathway. Among these subpathways, four genes (IGF1, MDM2, STAT1 and RAC1) were presumed to play an important role in bone GCT recurrence. The differentially expressed MDM2 protein was immunohistochemically confirmed in the recurrent versus primary bone GCT tissues. This study identified differentially expressed genes and their subpathways in recurrent GCT, which may serve as potential biomarkers for the prediction of GCT recurrence.
骨巨细胞瘤（GCT）是一种良性但具有局部侵袭性的骨肿瘤，极易发生局部复发和转移性疾病。因此，它为鉴定参与骨肿瘤进展和转移的生物学机制提供了一个有用的模型系统。本研究使用包含人类p53 80重分析板和人类干细胞80重分析板的QuantiGene 2.0多重分析阵列，对24例复发性与原发性骨GCT组织进行了分析。共鉴定出32个差异表达基因，包括复发性GCT中上调最多的20个基因和下调最多的12个基因。鉴定出的基因与细胞生长、黏附、凋亡、信号转导和骨形成有关。此外，进行了iSubpathwayMiner分析，以鉴定与该疾病相关的显著生物学通路区域（子通路）。通路分析确定了11个具有统计学意义的富集子通路，包括癌症通路、p53信号通路、破骨细胞分化通路和Wnt信号通路。在这些子通路中，四个基因（IGF1、MDM2、STAT1和RAC1）被认为在骨GCT复发中起重要作用。复发性与原发性骨GCT组织中差异表达的MDM2蛋白经免疫组织化学证实。本研究鉴定了复发性GCT中差异表达的基因及其子通路，它们可能作为预测GCT复发的潜在生物标志物。
