Prognostic value of the Hippo pathway transcriptional coactivators YAP/TAZ and β1-integrin in conventional osteosarcoma.
Prognostic value of the Hippo pathway transcriptional coactivators YAP/TAZ and β1-integrin in conventional osteosarcoma.
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DOI：
10.18632/oncotarget.11876
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发表时间：
2016-10-04
期刊：
影响因子：
--
通讯作者：
Salas S
中科院分区：
文献类型：
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作者：
Bouvier C;Macagno N;Nguyen Q;Loundou A;Jiguet-Jiglaire C;Gentet JC;Jouve JL;Rochwerger A;Mattei JC;Bouvard D;Salas S
目前，有关哺乳动物河马途径在骨肉瘤中的研究很少。YAP/TAZ转录共激活子是该途径的关键下游效应因子，也可能具有致癌特性。此外，最近的体外实验表明，β1整合素的表达促进了骨肉瘤的转移。本研究探讨YAP/TAZ和β-1整合素在人骨肉瘤中的表达。我们在组织微阵列(TMA)上进行了自动化免疫组织化学，其中69例化疗前进行的常规骨肉瘤活检被嵌入其中。用免疫反应记分(IRS)进行细胞定位和半定量分析，并与临床病理资料进行对照。β-1整合素在59例骨肉瘤中有54例(92%)呈胞浆表达，其中33例(56%)呈膜性染色。YAP/TAZ在骨肉瘤中表达27例(60%)，其中胞浆表达14例(31%)，核表达13例(28%)。未发现YAP/TAZ或β-1-整合素表达与化疗反应之间的联系。单因素分析显示，YAP/TAZ免疫反应评分与总生存期呈负相关(p=0.01)。β-1整合素在细胞膜上的表达也与OS有关(p=0.045)。在多因素分析中，YAP/TAZ核表达是PFS的独立预后因素(p=0.035)。本研究表明β-1-整合素和YAP/TAZ蛋白与预后有关，因此可能成为传统骨肉瘤的治疗靶点。
Currently, very few studies are available concerning the mammalian Hippo pathway in bone sarcomas. YAP/TAZ transcription co-activators are key downstream effectors of this pathway and may also have oncogenic properties. Additionally, recent in-vitro experiments showed that expression of β1-integrin promoted metastasis in osteosarcomas. This study investigated the expression of YAP/TAZ and β1-integrin in human osteosarcomas. We performed automated immunohistochemistry on tissue-microarrays (TMA) in which 69 conventional osteosarcomas biopsies performed prior to chemotherapy were embedded. Cellular localization and semi-quantitative analysis of each immunostain was performed using Immunoreactive Score (IRS) and correlated to clinico-pathological data. Cytoplasmic expression of β1-integrin was noted in 54/59 osteosarcomas (92%), with 33/59 cases (56%) displaying membranous staining. YAP/TAZ was expressed in 27/45 osteosarcomas (60%), with 14 cases (31%) showing cytoplasmic expression while 13 other cases (28%) displayed nuclear expression. No link was found between YAP/TAZ or β1-integrin expression and response to chemotherapy. In univariate analysis, YAP/TAZ immunoreactive score was pejoratively correlated with overall survival (p = 0.01). Expression of β1-integrin on cell membrane was also pejorative for OS (p = 0.045). In multivariate analysis, YAP/TAZ nuclear expression was an independent prognostic factor for PFS (p = 0.035). this study indicates that β1-integrin and YAP/TAZ proteins are linked to prognosis and therefore could be therapeutic targets in conventional osteosarcomas.