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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.
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http://dx.doi.org/10.1016/j.ccell.2018.12.003 | DOI Listing |
Research (Wash D C)
September 2025
Department of Urology, Fudan University Shanghai Cancer Center, State Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai 200433, China.
Collecting duct carcinoma (CDC) is a rare but aggressive form of renal cell carcinoma (RCC) that has limited understanding and an undefined systemic therapeutic regimen. Herein, we conducted a comprehensive proteogenomic analysis of CDC tumors and normal adjacent tissues to elucidate the biology of the disease. CDC exhibited high heterogeneity in tumor mutational burden, and enhanced ribosome biogenesis was the most striking malignant feature of CDC, even compared with other common kidney carcinomas.
View Article and Find Full Text PDFDiabetes
September 2025
Barbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus, Aurora, CO.
We developed a cell type-specific proteogenomic approach to reveal novel or unannotated open reading frames (nuORFs) using transcriptomics, ribosomal profiling, and proteomic analysis of human pancreatic β-cells using stem cell-derived β-cells and/or cadaveric islets. Our analysis revealed translational regulation of β-cell-specific pathways during differentiation and identified 965 nuORFs, with a majority exhibiting protein support and substantial β-cell specificity. A primate-specific ORF located in the 5' untranslated region of the type 1 diabetes risk gene TYK2 may act as a translational activator.
View Article and Find Full Text PDFCommun Biol
August 2025
Centre for Global Health Research, Usher Institute, University of Edinburgh, 5-7 Little France Road, Edinburgh, UK.
Understanding the genomic basis of human proteomic variability provides powerful tools to probe potential causal relationships of proteins and disease risk, and thus to prioritise candidate drug targets. Here, we investigated 6432 plasma proteins (1533 previously unstudied in large-scale proteomic GWAS) using the SomaLogic (v4.1) aptamer-based technology in a Scottish population from the Viking Genes study.
View Article and Find Full Text PDFBiochim Biophys Acta Mol Basis Dis
August 2025
Department of Human Anatomy and Cell Science, University of Manitoba College of Medicine, Winnipeg, Manitoba, Canada; Paul Albrechtsen Research Institute, CancerCare Manitoba, University of Manitoba, Winnipeg, Manitoba, Canada; Akademia Śląska, Katowice, Poland; Children Hospital Research Institut
This special volume of Biochimica et Biophysica Acta - Molecular Basis of Disease showcases a transformative era in biomedical research, driven by the convergence of multi-omics technologies, artificial intelligence (AI), and systems biology. The volume is focused across eight thematic sections-spanning cancer, inflammatory and infectious diseases, neurodegeneration, cardiovascular health, autophagy, respiratory disease, and heme biology-this volume highlights how integrative methodologies are helping to simplify the complexity of disease mechanisms. These studies discuss not only biomarker discovery and disease mechanisms, but also how redox biology, lipidomics, machine learning, and proteogenomics are redefining pathophysiological frameworks.
View Article and Find Full Text PDFSci Transl Med
August 2025
Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA.
Neurofibromin/NF1 is a RAS (rat sarcoma virus) GTPase-activating protein and estrogen receptor (ER) transcriptional corepressor. NF1 status, identified by copy number loss or low mRNA/protein expression, is associated with endocrine therapy resistance in ~20% of ER/HER2 (human epidermal growth factor receptor 2) early-stage breast cancers. The identification of targeted treatments for NF1 ER/HER2 breast cancer is therefore a priority.
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