Proteogenomic insights suggest druggable pathways in endometrial carcinoma
We characterized a prospective endometrial carcinoma (EC) cohort containing 138 tumors and 20 enriched normal tissues using 10 different omics platforms. Targeted quantitation of two peptides can predict antigen processing and presentation machinery activity, and may inform patient selection for immunotherapy. Association analysis between MYC activity and metformin treatment in both patients and cell lines suggests a potential role for metformin treatment in non-diabetic patients with elevated MYC activity. PIK3R1 in-frame indels are associated with elevated AKT phosphorylation and increased sensitivity to AKT inhibitors. CTNNB1 hotspot mutations are concentrated near phosphorylation sites mediating pS45-induced degradation of β-catenin, which may render Wnt-FZD antagonists ineffective. Deep learning accurately predicts EC subtypes and mutations from histopathology images, which may be useful for rapid diagnosis. Overall, this study identified molecular and imaging markers that can be further investigated to guide patient stratification for more precise treatment of EC.
Journal
Cancer CellFunding
iPGDAC, An Integrative Proteogenomic Data Analysis Center for CPTACProteogenomic Translational Research Center for Clinical ProteomicTranslating Pediatric Cancer Proteogenomic Data into Biological and Clinical InsightsThe Comprehensive Proteome Characterization Center at Johns Hopkins: High Precision Discovery and Confirmation of Genoproteomic TargetsUniversity of Michigan Rogel Cancer Center Support Grant 2023-2028Center for comprehensive proteogenomic data analysisProteogenomic Data Analysis for Cancer Systems Biology and Clinical TranslationPNNL Proteome Characterization CenterMichigan Center on Lifestage Environmental Exposures and Disease (M-LEEaD)Systems Biology based Proteogenomic Translator for Cancer Marker Discovery towards Precision MedicineIntegrated high throughput proteogenomic data analysis center for CPTACProteogenomic translator for cancer biomarker discovery towards precision medicineTranslational Breast Cancer Research Training ProgramTraining Program in Cell BiologyUniversity of Michigan Proteogenomics Data Analysis CenterCenter of Excellence for High Throughput Proteogenomic CharacterizationGenome Integrity Training ProgramCenter for Advanced Multi-Omic Characterization of CancerProteogenomic studies aimed at understanding ovarian tumor responses to agents targeting the DNA damage response and translating this knowledge into clinical benefitMICROSCALED PROTEOGENOMICS FOR CANCER CLINICAL TRIALSNational Cancer Institute Grant RR160027Translational Breast Cancer Research Training ProgramProteogenomic Data Analysis for Cancer Systems Biology and Clinical TranslationBattelle FundingCancer Prevention and Research Institute of Texas FundingU.S. Department of Defense Grant DOD BC220523U.S. Department of Energy Grant DE-AC05-76RL01830National Institutes of Health Grant 21X164QEndowment for Cardiometabolic Health Disparities ResearchProteogenomic studies aimed at understanding ovarian tumor responses to agents targeting the DNA damage response and translating this knowledge into clinical benefitProteogenomic Translational Research Center for Clinical ProteomicMICROSCALED PROTEOGENOMICS FOR CANCER CLINICAL TRIALSiPGDAC, An Integrative Proteogenomic Data Analysis Center for CPTACPNNL Proteome Characterization CenterUniversity of Michigan Proteogenomics Data Analysis CenterIntegrated high throughput proteogenomic data analysis center for CPTACThe Comprehensive Proteome Characterization Center at Johns Hopkins: High Precision Discovery and Confirmation of Genoproteomic TargetsCenter of Excellence for High Throughput Proteogenomic CharacterizationSystems Biology based Proteogenomic Translator for Cancer Marker Discovery towards Precision MedicineCenter for Advanced Multi-Omic Characterization of CancerTranslating Pediatric Cancer Proteogenomic Data into Biological and Clinical InsightsProteogenomic translator for cancer biomarker discovery towards precision medicinePacific Northwest National Laboratory Funding