Expression patterns of class I histone deacetylases in osteosarcoma: a novel prognostic marker with potential therapeutic implications.
Expression patterns of class I histone deacetylases in osteosarcoma: a novel prognostic marker with potential therapeutic implications.
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DOI：
10.1038/modpathol.2017.125
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发表时间：
2018-03
期刊：
影响因子：
--
通讯作者：
Settakorn J
中科院分区：
文献类型：
--
作者：
Chaiyawat P;Pruksakorn D;Phanphaisarn A;Teeyakasem P;Klangjorhor J;Settakorn J
表观遗传畸变被认为在癌症病因学和进展中具有关键作用。组蛋白脱乙酰酶是各种癌症类型中研究最多的表观遗传调节剂之一。采用免疫印迹技术，对患者来源的原代骨肉瘤细胞（6例）中I类组蛋白脱乙酰酶亚型1、2和3的表达水平进行了研究，并将其与正常骨移植物来源的成骨细胞（6例）进行比较。我们检测了89例高级别骨肉瘤组织中组蛋白去乙酰化酶的表达谱，并评估了其与临床病理参数和患者生存期的相关性。组蛋白去乙酰化酶在福尔马林固定的石蜡包埋的活检组织上进行化学染色。与良性成骨细胞相比，原代骨肉瘤细胞表达较高水平的组蛋白去乙酰化酶1和组蛋白去乙酰化酶2，但组蛋白去乙酰化酶3水平较低。总体而言，82，99和93%的89例骨肉瘤显示组蛋白去乙酰化酶亚型1，2和3的核表达，分别。低水平的组蛋白去乙酰化酶1与高Enneking分期（P=0.014）和初始转移（P=0.040）显著相关，而低水平的组蛋白去乙酰化酶3与年龄>15岁显著相关（P=0.026）。单因素生存分析发现Enneking分期高（P<0.001）、肿瘤轴位高（P=0.009）、有初发转移（P<0.001）、组蛋白去乙酰化酶1低表达（P=0.038）和全组蛋白去乙酰化酶低表达（P=0.016）的患者生存期明显缩短。多因素生存分析显示，只有轴位（P=0.011）和低全组蛋白去乙酰化酶表达（P=0.039）是独立的预后因素。在IIB期患者的亚组分析中（n=45），在单变量和多变量分析中，只有轴向位置和低全组蛋白脱乙酰酶表达与较短的生存期相关（轴向位置，P=0.008和0.010;低全HDAC，P=0.013和0.038）。低水平的全组蛋白去乙酰化酶表达与晚期疾病状态和短生存期显著相关。这些发现可能为将来组蛋白去乙酰化酶抑制剂在骨肉瘤患者中的应用提供指导。
Epigenetic aberrations are recognized as having pivotal roles in cancer etiology and progression. Histone deacetylases are among the most studied epigenetic modulators in various cancer types. The expression levels of class I histone deacetylase isoforms 1, 2, and 3 in patient-derived primary osteosarcoma cells (6 cases) was investigated, comparing them to normal bone graft-derived osteoblasts (6 cases) using the immunoblotting technique. Expression profiles of histone deacetylases in high-grade osteosarcoma tissue of 89 patients were examined and their association with clinicopathologic parameters and the patient survival was evaluated. Histone deacetylases were immunohistochemically stained on formalin-fixed paraffin-embedded biopsied tissue. Primary osteosarcoma cells expressed higher levels of histone deacetylase 1 and histone deacetylase 2, but lower levels of histone deacetylase 3 compared to benign osteoblasts. Overall, 82, 99, and 93% of 89 osteosarcomas showed nuclear expression of the histone deacetylase isoforms 1, 2, and 3, respectively. Low levels of histone deacetylase 1 were significantly associated with a high Enneking stage (P=0.014) and the presence of initial metastasis (P=0.040), while low levels of histone deacetylase 3 were significantly correlated with age >15 years (P=0.026). Univariate survival analysis found significantly shorter survival in the patients with a high Enneking stage (P<0.001), axial location (P=0.009), presence of initial metastasis (P<0.001), low-histone deacetylase 1 expression (P=0.038), and low-all-histone deacetylases expression (P=0.016). Multivariate survival analysis showed that only axial location (P=0.011) and low-all-histone deacetylases expression (P=0.039) were independent prognostic factors. In subgroup analysis of stage IIB patients (n=45), only axial location and low-all-histone deacetylases expression were associated with shorter survival in both univariate and multivariate analysis (axial location, P=0.008 and 0.010; low-all-HDACs, P=0.013 and 0.038, respectively). Low levels of all-histone deacetylases expression were significantly associated with advanced disease status and short survival. These findings may be a guide to future use of histone deacetylase inhibitors in osteosarcoma patients.
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影响因子：
2.4
作者：
Seo J;Min SK;Park HR;Kim DH;Kwon MJ;Kim LS;Ju YS
通讯作者：
Ju YS
影响因子：
--
作者：
Cain JE;McCaw A;Jayasekara WS;Rossello FJ;Marini KD;Irving AT;Kansara M;Thomas DM;Ashley DM;Watkins DN
通讯作者：
Watkins DN
影响因子：
5.2
作者：
Pruksakorn D;Teeyakasem P;Klangjorhor J;Chaiyawat P;Settakorn J;Diskul-Na-Ayudthaya P;Chokchaichamnankit D;Pothacharoen P;Srisomsap C
通讯作者：
Srisomsap C
影响因子：
--
作者：
Allison DC;Carney SC;Ahlmann ER;Hendifar A;Chawla S;Fedenko A;Angeles C;Menendez LR
通讯作者：
Menendez LR
影响因子：
5.3
作者：
Escaffit, Fabrice;Vaute, Olivier;Trouche, Didier
通讯作者：
Trouche, Didier