The diffuse-type gastric cancer (DGC) is a subtype of gastric cancer with the worst prognosis and few treatment options. Here we present a dataset from 84 DGC patients, composed of a proteome of 11,340 gene products and mutation information of 274 cancer driver genes covering paired tumor and nearby tissue. DGC can be classified into three subtypes (PX1–3) based on the altered proteome alone. PX1 and PX2 exhibit dysregulation in the cell cycle and PX2 features an additional EMT process; PX3 is enriched in immune response proteins, has the worst survival, and is insensitive to chemotherapy. Data analysis revealed four major vulnerabilities in DGC that may be targeted for treatment, and allowed the nomination of potential immunotherapy targets for DGC patients, particularly for those in PX3. This dataset provides a rich resource for information and knowledge mining toward altered signaling pathways in DGC and demonstrates the benefit of proteomic analysis in cancer molecular subtyping.

Transcription factors (TFs) drive various biological processes ranging from embryonic development to carcinogenesis. Here, we employ a recently developed concatenated tandem array of consensus TF response elements (catTFRE) approach to profile the activated TFs in 24 adult and 8 fetal mouse tissues on proteome scale. A total of 941 TFs are quantitatively identified, representing over 60% of the TFs in the mouse genome. Using an integrated omics approach, we present a TF network in the major organs of the mouse, allowing data mining and generating knowledge to elucidate the roles of TFs in various biological processes, including tissue type maintenance and determining the general features of a physiological system. This study provides a landscape of TFs in mouse tissues that can be used to elucidate transcriptional regulatory specificity and programming and as a baseline that may facilitate understanding diseases that are regulated by TFs.

The mammalian stomach is structurally highly diverse and its organ functionality critically depends on a normal embryonic development. Although there have been several studies on the morphological changes during stomach development, a system-wide analysis of the underlying molecular changes is lacking. Here, we present a comprehensive, temporal proteome and transcriptome atlas of the mouse stomach at multiple developmental stages. Quantitative analysis of 12,108 gene products allows identifying three distinct phases based on changes in proteins and RNAs and the gain of stomach functions on a longitudinal time scale. The transcriptome indicates functionally important isoforms relevant to development and identifies several functionally unannotated novel splicing junction transcripts that we validate at the peptide level. Importantly, many proteins differentially expressed in stomach development are also significantly overexpressed in diffuse-type gastric cancer. Overall, our study provides a resource to understand stomach development and its connection to gastric cancer tumorigenesis.

Liver organogenesis and development are composed of a series of complex, well-orchestrated events. Identifying key factors and pathways governing liver development will help elucidate the physiological and pathological processes including those of cancer. We conducted multidimensional omics measurements including protein, mRNA, and transcription factor (TF) DNA-binding activity for mouse liver tissues collected from embryonic day 12.5 (E12.5) to postnatal week 8 (W8), encompassing major developmental stages. These data sets reveal dynamic changes of core liver functions and canonical signaling pathways governing development at both mRNA and protein levels. The TF DNA-binding activity data set highlights the importance of TF activity in early embryonic development. A comparison between mouse liver development and human hepatocellular carcinoma (HCC) proteomic profiles reveal that more aggressive tumors are characterized with the activation of early embryonic development pathways, whereas less aggressive ones maintain liver function–related pathways that are elevated in the mature liver. This work offers a panoramic view of mouse liver development and provides a rich resource to explore in-depth functional characterization.