Comprehensive proteome analysis of pancreatic cancers for understanding the mechanisms of carcinogenesis and cancer metastasis

许多胰腺癌患者在初次就诊时已转移到远处器官。 本研究的目的是从蛋白质组水平了解胰腺癌转移的机制，为建立一种新的生物标志物做出贡献。 为了解决这个问题，我们采用了一个模型系统，其中比较了从单个患者的三个转移部位（肝、肺和腹膜）分离的细胞。 我们使用了SILAC为基础的精确定量蛋白质组学策略结合高分辨率质谱分析的总蛋白质组和酪氨酸磷酸化蛋白质组的每个转移。 我们的数据揭示了在三种不同的转移性病变中，整体蛋白质组表达以及酪氨酸激酶活性的不同模式。 这种异质性是显著的，因为它导致肿瘤细胞对靶向各种激酶和其他途径的小分子抑制剂的不同敏感性。

Many patients with pancreatic cancer have metastases to distant organs at the time of initial presentation. The goal of this study is to understand the mechanisms of pancreatic cancer metastasis at the proteome level, contributing to create a novel biomarker. To address, we employed a model system in which cells isolated from three sites of metastasis (liver, lung and peritoneum) from a single patient were compared. We used a SILAC-based accurate quantitative proteomic strategy combined with a high resolution mass spectrometry to analyze the total proteome and tyrosine phosphoproteome of each of the metastases. Our data revealed distinct patterns of both overall proteome expression as well as tyrosine kinase activities across the three different metastatic lesions. This heterogeneity is significant because it led to differential sensitivity of the neoplastic cells to small molecule inhibitors targeting various kinases and other pathways.