Identification of AFAP1L1 as a prognostic marker for spindle cell sarcomas
Identification of AFAP1L1 as a prognostic marker for spindle cell sarcomas
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DOI：
10.1038/onc.2011.108
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发表时间：
2011-09-01
期刊：
影响因子：
8
通讯作者：
Toguchida, J.
中科院分区：
文献类型：
--
作者：
Furu, M.;Kajita, Y.;Toguchida, J.
梭形细胞肉瘤是由不同生物学特性的肿瘤组成，其中远处转移是预后不良的最不祥征兆。然而，转移是很难预测的基础上，目前的组织病理学分析。我们从65例梭形细胞肉瘤的基因表达谱中确定了肌动蛋白毒力相关蛋白1样1（AFAP 1 L1）作为转移预测标志物的候选者。多变量分析确定AFAP 1 L1是预测远处转移发生的独立因素（P = 0.0001），这在另一组41例肿瘤中通过定量mRNA表达分析进一步证实。使用石蜡包埋的肿瘤组织进行的免疫组化染色显示，AFAP 1 L1阴性的肿瘤的无转移率显著更好（对数秩检验P = 0.0093）。在肉瘤细胞中敲除AFAP 1 L1基因导致细胞侵袭的抑制，并且在永生化的人间充质干细胞中强制表达AFAP 1 L1诱导了锚定非依赖性生长，并且增加了具有高活性水平的基质金属肽酶的细胞侵袭力。此外，在AFAP 1 L1转导的肉瘤细胞系中，体内肿瘤生长加速。这些结果表明，AFAP 1 L1在梭形细胞肉瘤的进展中起作用，是一种预后生物标志物。Oncogene（2011）30，4015-4025; doi：10.1038/onc.2011.108; 2011年4月25日在线发表
Spindle cell sarcomas consist of tumors with different biological features, of which distant metastasis is the most ominous sign for a poor prognosis. However, metastasis is difficult to predict on the basis of current histopathological analyses. We have identified actin filament-associated protein 1-like 1 (AFAP1L1) as a candidate for a metastasis-predicting marker from the gene expression profiles of 65 spindle cell sarcomas. A multivariate analysis determined that AFAP1L1 was an independent factor for predicting the occurrence of distant metastasis (P = 0.0001), which was further confirmed in another set of 41 tumors by a quantitative mRNA expression analysis. Immunohistochemical staining using paraffin-embedded tumor tissues revealed that the metastasis-free rate was significantly better in tumors negative for AFAP1L1 (P = 0.0093 by log-rank test). Knocking down the AFAP1L1 gene in sarcoma cells resulted in inhibition of the cell invasion, and forced expression of AFAP1L1 in immortalized human mesenchymal stem cells induced anchorage-independent growth and increased cell invasiveness with high activity levels of matrix metallo-peptidase. Furthermore, tumor growth in vivo was accelerated in AFAP1L1-transduced sarcoma cell lines. These results suggest that AFAP1L1 has a role in the progression of spindle cell sarcomas and is a prognostic biomarker. Oncogene (2011) 30, 4015-4025; doi:10.1038/onc.2011.108; published online 25 April 2011