Loss of the CBX7 protein expression correlates with a more aggressive phenotype in pancreatic cancer
Loss of the CBX7 protein expression correlates with a more aggressive phenotype in pancreatic cancer
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DOI：
10.1016/j.ejca.2010.01.033
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发表时间：
2010-05-01
影响因子：
8.4
通讯作者：
Fusco, Alfredo
中科院分区：
文献类型：
--
作者：
Karamitopoulou, Eva;Pallante, Pierlorenzo;Fusco, Alfredo
多梳组（PcG）蛋白作为多蛋白复合物发挥作用，是基因调控机制的一部分，决定细胞在正常和致病发育过程中的命运。胰腺导管腺癌是一种侵袭性肿瘤，通过称为胰腺上皮内瘤变（PanIN）的前病变，遵循多步骤的进展模式本研究旨在探讨PcG蛋白CBX 7在胰腺癌发生发展中的作用及其在胰腺癌诊断和预后判断中的意义。CBX 7在210例胰腺导管腺癌中的表达，这些胰腺导管腺癌来自切除标本，结合在组织微阵列（TMA）上，包括另外40例PanIN病例和40例正常对照。采用受试者工作特征（ROC）曲线分析法对结果进行评价，并与肿瘤的临床病理参数和患者的预后进行相关性分析。CBX 7蛋白在正常胰腺组织、PanINs和浸润性导管腺癌中的表达存在显著差异，且呈进行性降低。CBX 7表达的缺失与胰腺癌恶性程度的增加相关，而CBX 7表达的维持显示出生存期延长的趋势。此外，E-cadherin表达的缺失与CBX 7的缺失相关，并与患者生存率下降的趋势相关。这些结果表明，CBX 7在胰腺癌发生中起作用，其表达的缺失与更具侵袭性的表型相关。(C)2010爱思唯尔有限公司版权所有。
Polycomb group (PcG) proteins function as multiprotein complexes and are part of a gene regulatory mechanism that determines cell fate during normal and pathogenic development. Several studies have implicated the deregulation of different PcG proteins in neoplastic progression.Pancreatic ductal adenocarcinoma is an aggressive neoplasm that follows a multistep model of progression through precursor lesions called pancreatic intraepithelial neoplasia (PanIN).Aim of this study was to investigate the role of PcG protein CBX7 in pancreatic carcinogenesis and to evaluate its possible diagnostic and prognostic significance.We analysed by immunohistochemistry the expression of CBX7 in 210 ductal pancreatic adenocarcinomas from resection specimens, combined on a tissue microarray (TMA) including additional 40 PanIN cases and 40 normal controls. The results were evaluated by using receiver operating characteristic (ROC) curve analysis for the selection of cut-off scores and correlated to the clinicopathological parameters of the tumours and the outcome of the patients. Expression of E-cadherin, a protein positively regulated by CBX7, was also assessed.A significantly differential, and progressively decreasing CBX7 protein expression was found between normal pancreatic tissue, PanINs and invasive ductal adenocarcinoma. Loss of CBX7 expression was associated with increasing malignancy grade in pancreatic adenocarcinoma, whereas the maintenance of CBX7 expression showed a trend toward a longer survival. Moreover, loss of E-cadherin expression was associated with loss of CBX7 and with a trend towards worse patient survival.These results suggest that CBX7 plays a role in pancreatic carcinogenesis and that its loss of expression correlates to a more aggressive phenotype. (C) 2010 Elsevier Ltd. All rights reserved.