Department of Pathology, All India Institute of Medical Sciences, New Delhi 110029, India.
Department of Neurosurgery, All India Institute of Medical Sciences, New Delhi 110029, India.
Hum Pathol. 2018 Dec;82:149-157. doi: 10.1016/j.humpath.2018.07.018. Epub 2018 Jul 29.
Epithelial-to-mesenchymal transition (EMT) plays an important role in invasion and metastasis of various cancers including gliomas. EMT has also been linked to cancer stem cells and resistance to chemotherapy. An initial in-silico data mining in a published ependymoma (EPN) patient series (GSE21687) revealed up-regulation of EMT transcription factors in tumor samples. Furthermore, quantitative real-time polymerase chain reaction-based gene expression analysis of EMT transcription factors in 96 EPNs showed significant up-regulation of SNAI1, SNAI2, ZEB1, and TWIST1 as compared with normal brain, associated with up-regulation of CDH2/N-cadherin and down-regulation of CDH1/E-cadherin. Although this was observed in varying degrees in all clinicopathological-molecular subgroups of EPNs, it was most evident in supratentorial EPNs harboring fusions of RELA (v-rel avian reticuloendotheliosis viral oncogene homolog A) gene and in posterior fossa EPNs. Immunohistochemistry performed in 60 of the above cases corroborated with gene expression patterns, and immunopositivity for Snail, Slug, Zeb1, and Twist1 was observed in 80%, 80%, 81%, and 63% of all EPNs. Immunopositivity for N-cadherin and E-cadherin was observed in 76.6% and 2% of the cases, respectively. Univariate Cox regression analysis showed that low expression of CDH1/E-cadherin (P = .002) and high expression levels of CDH2/N-cadherin (P < .001), SNAI1/Snail (P = .023), SNAI2/Slug (P < .001), and ZEB1 (P < .001) were associated with shorter progression-free survival. Here, we report for the first time the existence of EMT-like phenotype in EPNs. These factors could represent new prognostic and therapeutic targets in EPN.
上皮间质转化 (EMT) 在包括神经胶质瘤在内的各种癌症的侵袭和转移中起着重要作用。EMT 也与癌症干细胞和化疗耐药有关。在一个已发表的室管膜瘤 (EPN) 患者系列 (GSE21687) 的初步计算机数据挖掘中，发现肿瘤样本中 EMT 转录因子上调。此外，对 96 例 EPN 中 EMT 转录因子的定量实时聚合酶链反应基因表达分析显示，与正常脑相比，SNAI1、SNAI2、ZEB1 和 TWIST1 显著上调，与 CDH2/N-钙粘蛋白上调和 CDH1/E-钙粘蛋白下调相关。尽管在 EPN 的所有临床病理分子亚组中都观察到了不同程度的这种情况，但在携带 RELA（v-rel 禽网状内皮增生病毒致癌基因同源物 A）基因融合的幕上 EPN 和后颅窝 EPN 中最为明显。在上述 60 例病例中进行的免疫组织化学检查与基因表达模式相符，并且在所有 EPN 中观察到 Snail、Slug、Zeb1 和 Twist1 的免疫阳性率分别为 80%、80%、81%和 63%。N-钙粘蛋白和 E-钙粘蛋白的免疫阳性率分别为 76.6%和 2%。单变量 Cox 回归分析显示，CDH1/E-钙粘蛋白低表达 (P = .002) 和 CDH2/N-钙粘蛋白高表达 (P < .001)、SNAI1/Snail (P = .023)、SNAI2/Slug (P < .001) 和 ZEB1 (P < .001) 与无进展生存期较短相关。在这里，我们首次报道了 EPN 中 EMT 样表型的存在。这些因素可能代表 EPN 中新的预后和治疗靶点。
