PDF(Pubmed)
Abstract：
Cadherins are cell-cell adhesion proteins which have been strongly implicated in cancer invasion, dissemination and metastasis capacity; thus, they are key players in the epithelial-to-mesenchymal transition (EMT) program. However, their role in glioblastoma (GBM), a primary central nervous system aggressive tumor, remains to be clarified. N-, E- and P-cadherin expression was analyzed on a large series of GBMs, characterized with clinical, imaging and neuropathological parameters, as well as with patients\' survival data. In addition, cadherins\' expression was studied in match-recurrent cases. Using TCGA data, cadherin expression profiles were also evaluated according to GBM transcription subtypes. N-cadherin expression was observed in 81.5% of GBM, followed by E-cadherin in 31% and P-cadherin in 20.8%. Upon tumor recurrence, P-cadherin was the only significantly upregulated cadherin compared with the primary tumor, being positive in 65.8% of the cases. Actually, P-cadherin gain was observed in 51.4% of matched primary-recurrent cases. Cadherins\' co-expression was also explored. Interestingly, E- and N-cadherin co-expression identified a GBM subgroup with frequent epithelial differentiation and a significant survival benefit. On the other hand, subgroups with P-cadherin expression carried the worse prognosis. P- and N-cadherin co-expression correlated with the presence of a mesenchymal phenotype. Expressions of isolated P-cadherin or E- and P-cadherin co-expression were associated with imaging characteristics of aggressiveness, to highly heterogeneous tumors, an d to worse patient survival. Classical cadherins co-expression subgroups present consistent clinical, imaging, neuropathological and survival differences, which probably reflect different states of an EMT-like program in GBM.
摘要：
钙黏着蛋白是细胞-细胞粘附蛋白，与癌症侵袭密切相关。传播和转移能力；因此，他们是上皮间质转化（EMT）计划的关键参与者。然而,它们在胶质母细胞瘤（GBM）中的作用，原发性中枢神经系统侵袭性肿瘤,还有待澄清。N-,在一系列GBM上分析了E-和P-cadherin的表达，以临床为特征，影像学和神经病理学参数，以及患者的生存数据。此外,在匹配复发病例中研究了钙黏着蛋白的表达。使用TCGA数据，还根据GBM转录亚型评估钙粘蛋白表达谱。在81.5%的GBM中观察到N-cadherin表达,其次是E-cadherin占31%，P-cadherin占20.8%。肿瘤复发后，P-cadherin是与原发肿瘤相比唯一显著上调的cadherin,65.8%的病例呈阳性。事实上,在51.4％的匹配原发性复发病例中观察到P-cadherin增加。还探索了钙粘着蛋白的共表达。有趣的是,E-和N-钙黏着蛋白共表达鉴定了具有频繁上皮分化和显著存活益处的GBM亚组。另一方面,具有P-cadherin表达的亚组预后较差。P-和N-钙粘蛋白共表达与间充质表型的存在相关。分离的P-cadherin或E-和P-cadherin共表达与侵袭性的影像学特征有关，高度异质性的肿瘤，d使病人的生存率更差。经典钙黏着蛋白共表达亚组呈现一致的临床，成像,神经病理学和生存差异，这可能反映了GBM中类似EMT程序的不同状态。
