Department of Chemistry, Center for Proteogenome Research, Korea University, Seoul 136-701, Republic of Korea.
Department of New Biology and Center for Plant Aging Research, Institute for Basic Science, DGIST, Daegu 711-873, Republic of Korea; Division of Molecular Pathology, Oncode Institute, the Netherlands Cancer Institute, 1066CX Amsterdam, the Netherlands.
Cancer Cell. 2019 Jan 14;35(1):111-124.e10. doi: 10.1016/j.ccell.2018.12.003.
We report proteogenomic analysis of diffuse gastric cancers (GCs) in young populations. Phosphoproteome data elucidated signaling pathways associated with somatic mutations based on mutation-phosphorylation correlations. Moreover, correlations between mRNA and protein abundances provided potential oncogenes and tumor suppressors associated with patient survival. Furthermore, integrated clustering of mRNA, protein, phosphorylation, and N-glycosylation data identified four subtypes of diffuse GCs. Distinguishing these subtypes was possible by proteomic data. Four subtypes were associated with proliferation, immune response, metabolism, and invasion, respectively; and associations of the subtypes with immune- and invasion-related pathways were identified mainly by phosphorylation and N-glycosylation data. Therefore, our proteogenomic analysis provides additional information beyond genomic analyses, which can improve understanding of cancer biology and patient stratification in diffuse GCs.
我们报告了青年人群弥漫性胃癌(GC)的蛋白质基因组分析。磷酸化蛋白质组数据根据突变-磷酸化相关性阐明了与体细胞突变相关的信号通路。此外,mRNA 和蛋白质丰度之间的相关性提供了与患者生存相关的潜在癌基因和肿瘤抑制因子。此外,mRNA、蛋白质、磷酸化和 N-糖基化数据的综合聚类鉴定了四种弥漫性 GC 亚型。通过蛋白质组学数据可以区分这些亚型。四种亚型分别与增殖、免疫反应、代谢和侵袭有关;通过磷酸化和 N-糖基化数据主要确定了亚型与免疫和侵袭相关途径的关联。因此,我们的蛋白质基因组分析提供了基因组分析之外的附加信息,这可以提高对弥漫性 GC 中癌症生物学和患者分层的理解。