Most molecular cancer therapies act on protein targets but data on the proteome status of patients and cellular models for proteome-guided pre-clinical drug sensitivity studies are only beginning to emerge. Here, we profiled the proteomes of 65 colorectal cancer (CRC) cell lines to a depth of > 10,000 proteins using mass spectrometry. Integration with proteomes of 90 CRC patients and matched transcriptomics data defined integrated CRC subtypes, highlighting cell lines representative of each tumour subtype. Modelling the responses of 52 CRC cell lines to 577 drugs as a function of proteome profiles enabled predicting drug sensitivity for cell lines and patients. Among many novel associations, MERTK was identified as a predictive marker for resistance towards MEK1/2 inhibitors and immunohistochemistry of 1,074 CRC tumours confirmed MERTK as a prognostic survival marker. We provide the proteomic and pharmacological data as a resource to the community to, for example, facilitate the design of innovative prospective clinical trials.

中文翻译：

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人类结肠癌和直肠癌的药代动力学表征。

大多数分子癌症疗法都作用于蛋白质靶标，但是有关患者蛋白质组状态的数据以及用于蛋白质组学指导的临床前药物敏感性研究的细胞模型才刚刚开始出现。在这里，我们使用质谱分析了65种结直肠癌（CRC）细胞系的蛋白质组，其蛋白质组的深度> 10,000。与90名CRC患者的蛋白质组整合以及匹配的转录组学数据定义了整合的CRC亚型，突出了代表每种肿瘤亚型的细胞系。根据蛋白质组谱对52种CRC细胞对577种药物的反应进行建模，可以预测细胞系和患者的药物敏感性。在许多新的关联中，MERTK被确定为对MEK1 / 2抑制剂和1的免疫组织化学的抵抗力的预测标志物 074例CRC肿瘤证实MERTK是预后的生存指标。我们向社区提供蛋白质组学和药理学数据，作为资源，例如，促进创新性前瞻性临床试验的设计。