Discovery of New Molecular Subtypes in Oesophageal Adenocarcinoma
Discovery of New Molecular Subtypes in Oesophageal Adenocarcinoma
复制标题
DOI：
10.1371/journal.pone.0023985
复制
发表时间：
2011-09-23
期刊：
影响因子：
3.7
通讯作者：
Becker, Karl-Friedrich
中科院分区：
文献类型：
--
作者：
Berg, Daniela;Wolff, Claudia;Becker, Karl-Friedrich
大量患有食管腺癌的患者对常规化疗没有反应;因此，有必要鉴定新的预测性生物标志物和患者特征以改善患者结局和治疗选择。我们分析了87福尔马林固定和石蜡包埋（FFPE）食管腺癌组织样本与反相蛋白质阵列（RPPA）检查17个癌症相关的信号分子的表达。蛋白质表达水平通过无监督分层聚类进行分析，并与临床病理参数和患者总体生存率相关。蛋白质组学分析揭示了一种新的，非常有前途的分子亚型食管腺癌患者的特点是低水平的HSP 27家族蛋白和高表达的HER家族阳性淋巴结，远处转移和短的总生存期。在其他独立研究中得到证实后，我们的结果可能是为这个新的食管腺癌患者亚组开发Her 2靶向治疗方案的基础。
A large number of patients suffering from oesophageal adenocarcinomas do not respond to conventional chemotherapy; therefore, it is necessary to identify new predictive biomarkers and patient signatures to improve patient outcomes and therapy selections. We analysed 87 formalin-fixed and paraffin-embedded (FFPE) oesophageal adenocarcinoma tissue samples with a reverse phase protein array (RPPA) to examine the expression of 17 cancer-related signalling molecules. Protein expression levels were analysed by unsupervised hierarchical clustering and correlated with clinicopathological parameters and overall patient survival. Proteomic analyses revealed a new, very promising molecular subtype of oesophageal adenocarcinoma patients characterised by low levels of the HSP27 family proteins and high expression of those of the HER family with positive lymph nodes, distant metastases and short overall survival. After confirmation in other independent studies, our results could be the foundation for the development of a Her2-targeted treatment option for this new patient subgroup of oesophageal adenocarcinoma.