跨人类癌症的膜蛋白调节网络。

Membrane protein-regulated networks across human cancers.

机构信息

Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsinchu, 300, Taiwan.

Bioinformatics Center, Institute for Chemical Research, Kyoto University, Kyoto, 611-0011, Japan.

出版信息

Nat Commun. 2019 Jul 16;10(1):3131. doi: 10.1038/s41467-019-10920-8.

Alterations in membrane proteins (MPs) and their regulated pathways have been established as cancer hallmarks and extensively targeted in clinical applications. However, the analysis of MP-interacting proteins and downstream pathways across human malignancies remains challenging. Here, we present a systematically integrated method to generate a resource of cancer membrane protein-regulated networks (CaMPNets), containing 63,746 high-confidence protein-protein interactions (PPIs) for 1962 MPs, using expression profiles from 5922 tumors with overall survival outcomes across 15 human cancers. Comprehensive analysis of CaMPNets links MP partner communities and regulated pathways to provide MP-based gene sets for identifying prognostic biomarkers and druggable targets. For example, we identify CHRNA9 with 12 PPIs (e.g., ERBB2) can be a therapeutic target and find its anti-metastasis agent, bupropion, for treatment in nicotine-induced breast cancer. This resource is a study to systematically integrate MP interactions, genomics, and clinical outcomes for helping illuminate cancer-wide atlas and prognostic landscapes in tumor homo/heterogeneity.

膜蛋白 (MPs) 的改变及其调控途径已被确定为癌症的标志，并在临床应用中得到广泛靶向。然而，分析人类恶性肿瘤中的 MPs 相互作用蛋白及其下游途径仍然具有挑战性。在这里，我们提出了一种系统的综合方法，使用来自 15 种人类癌症中 5922 个具有总生存结果的肿瘤的表达谱，生成了一个包含 1962 个 MPs 的癌症膜蛋白调控网络 (CaMPNets) 的资源，其中包含 63746 个高可信度的蛋白质-蛋白质相互作用 (PPIs)。对 CaMPNets 的综合分析将 MPs 伙伴社区和调控途径联系起来，提供基于 MPs 的基因集，用于识别预后生物标志物和可用药靶。例如，我们发现具有 12 个 PPIs（如 ERBB2）的 CHRNA9 可以作为治疗靶点，并找到了其抗转移剂丁丙诺啡，用于治疗尼古丁诱导的乳腺癌。该资源是对 MPs 相互作用、基因组学和临床结果进行系统整合的一项研究，有助于阐明肿瘤同/异质性中的癌症全图谱和预后景观。