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.
钙黏蛋白是介导细胞间黏附的蛋白质，在肿瘤侵袭、播散和转移过程中发挥关键作用，是上皮-间质转化程序的核心调控因子。然而，其在原发性中枢神经系统侵袭性肿瘤——胶质母细胞瘤中的作用机制尚未明确。本研究通过对大样本GBM病例进行钙黏蛋白表达分析，并结合临床特征、影像学参数、神经病理学指标及患者生存数据，系统探讨了N-、E-和P-钙黏蛋白的表达模式。同时，在配对复发样本中检测了钙黏蛋白的动态变化。基于TCGA数据库，进一步分析了不同GBM转录亚型中钙黏蛋白的表达谱特征。 研究结果显示：81.5%的GBM样本表达N-钙黏蛋白，E-钙黏蛋白和P-钙黏蛋白的表达率分别为31%和20.8%。在肿瘤复发过程中，P-钙黏蛋白是唯一显著上调的亚型，65.8%的复发样本呈阳性表达。在配对的原发-复发样本中，51.4%的病例出现P-钙黏蛋白表达增益。钙黏蛋白共表达模式分析发现：E-与N-钙黏蛋白共表达的GBM亚群常呈现上皮分化特征，且患者生存期显著延长；而表达P-钙黏蛋白的亚群预后最差。P-与N-钙黏蛋白共表达与间质表型密切相关。单独P-钙黏蛋白表达或E/P-钙黏蛋白共表达均与侵袭性影像学特征、高度异质性肿瘤表型及不良生存预后显著相关。 研究表明，经典钙黏蛋白的共表达模式可界定具有显著差异的临床-影像-病理-预后特征的GBM亚群，这很可能反映了GBM中上皮-间质转化样程序的不同活化状态。
Cadherin Expression Profiles Define Glioblastoma Differentiation and Patient Prognosis
肿瘤(癌症)患者之家