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Proteogenomic analysis of lung adenocarcinoma reveals tumor heterogeneity, survival determinants, and therapeutically relevant pathways.
Soltis, Anthony R; Bateman, Nicholas W; Liu, Jianfang; Nguyen, Trinh; Franks, Teri J; Zhang, Xijun; Dalgard, Clifton L; Viollet, Coralie; Somiari, Stella; Yan, Chunhua; Zeman, Karen; Skinner, William J; Lee, Jerry S H; Pollard, Harvey B; Turner, Clesson; Petricoin, Emanuel F; Meerzaman, Daoud; Conrads, Thomas P; Hu, Hai; Shriver, Craig D; Moskaluk, Christopher A; Browning, Robert F; Wilkerson, Matthew D.
Afiliación
  • Soltis AR; The American Genome Center, Collaborative Health Initiative Research Program, Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA; Henry M. Jackson Foundation for Military Medicine, Bethesda, MD 20817, USA.
  • Bateman NW; Henry M. Jackson Foundation for Military Medicine, Bethesda, MD 20817, USA; Women's Health Integrated Research Center, Inova Women's Service Line, Inova Fairfax Medical Campus, Falls Church, VA 22042, USA; Gynecologic Cancer Center of Excellence, Murtha Cancer Center Research Program, Uniformed Serv
  • Liu J; Chan Soon-Shiong Institute of Molecular Medicine at Windber, Windber, PA 15963, USA.
  • Nguyen T; Center for Biomedical Informatics and Information Technology, National Cancer Institute, Rockville, MD 20850, USA.
  • Franks TJ; Pulmonary and Mediastinal Pathology, Department of Defense, Joint Pathology Center, Silver Spring, MD 20910, USA.
  • Zhang X; The American Genome Center, Collaborative Health Initiative Research Program, Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA; Henry M. Jackson Foundation for Military Medicine, Bethesda, MD 20817, USA.
  • Dalgard CL; The American Genome Center, Collaborative Health Initiative Research Program, Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
  • Viollet C; The American Genome Center, Collaborative Health Initiative Research Program, Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA; Henry M. Jackson Foundation for Military Medicine, Bethesda, MD 20817, USA.
  • Somiari S; Chan Soon-Shiong Institute of Molecular Medicine at Windber, Windber, PA 15963, USA.
  • Yan C; Center for Biomedical Informatics and Information Technology, National Cancer Institute, Rockville, MD 20850, USA.
  • Zeman K; Department of Medicine, Walter Reed National Military Medical Center, Bethesda, MD 20814, USA; John P. Murtha Cancer Center Research Program, Uniformed Services University, Bethesda, MD 20814, USA.
  • Skinner WJ; Department of Medicine, Walter Reed National Military Medical Center, Bethesda, MD 20814, USA; John P. Murtha Cancer Center Research Program, Uniformed Services University, Bethesda, MD 20814, USA.
  • Lee JSH; Henry M. Jackson Foundation for Military Medicine, Bethesda, MD 20817, USA; John P. Murtha Cancer Center Research Program, Uniformed Services University, Bethesda, MD 20814, USA; Lawrence J. Ellison Institute for Transformative Medicine, Los Angeles, CA 90064, USA; Departments of Medicine, Chemical
  • Pollard HB; The American Genome Center, Collaborative Health Initiative Research Program, Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
  • Turner C; John P. Murtha Cancer Center Research Program, Uniformed Services University, Bethesda, MD 20814, USA.
  • Petricoin EF; Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA 20110, USA.
  • Meerzaman D; Center for Biomedical Informatics and Information Technology, National Cancer Institute, Rockville, MD 20850, USA.
  • Conrads TP; Women's Health Integrated Research Center, Inova Women's Service Line, Inova Fairfax Medical Campus, Falls Church, VA 22042, USA; Gynecologic Cancer Center of Excellence, Murtha Cancer Center Research Program, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
  • Hu H; Chan Soon-Shiong Institute of Molecular Medicine at Windber, Windber, PA 15963, USA; John P. Murtha Cancer Center Research Program, Uniformed Services University, Bethesda, MD 20814, USA.
  • Shriver CD; John P. Murtha Cancer Center Research Program, Uniformed Services University, Bethesda, MD 20814, USA. Electronic address: craig.shriver@usuhs.edu.
  • Moskaluk CA; Department of Pathology, University of Virginia, Charlottesville, VA 22908, USA. Electronic address: cam5p@virginia.edu.
  • Browning RF; Department of Medicine, Walter Reed National Military Medical Center, Bethesda, MD 20814, USA; John P. Murtha Cancer Center Research Program, Uniformed Services University, Bethesda, MD 20814, USA. Electronic address: robert.f.browning2.civ@health.mil.
  • Wilkerson MD; The American Genome Center, Collaborative Health Initiative Research Program, Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA. Electronic address: matthew.wilkerson@usuhs.edu.
Cell Rep Med ; 3(11): 100819, 2022 11 15.
Article en En | MEDLINE | ID: mdl-36384096
We present a deep proteogenomic profiling study of 87 lung adenocarcinoma (LUAD) tumors from the United States, integrating whole-genome sequencing, transcriptome sequencing, proteomics and phosphoproteomics by mass spectrometry, and reverse-phase protein arrays. We identify three subtypes from somatic genome signature analysis, including a transition-high subtype enriched with never smokers, a transversion-high subtype enriched with current smokers, and a structurally altered subtype enriched with former smokers, TP53 alterations, and genome-wide structural alterations. We show that within-tumor correlations of RNA and protein expression associate with tumor purity and immune cell profiles. We detect and independently validate expression signatures of RNA and protein that predict patient survival. Additionally, among co-measured genes, we found that protein expression is more often associated with patient survival than RNA. Finally, integrative analysis characterizes three expression subtypes with divergent mutations, proteomic regulatory networks, and therapeutic vulnerabilities. This proteogenomic characterization provides a foundation for molecularly informed medicine in LUAD.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteogenómica / Adenocarcinoma del Pulmón / Neoplasias Pulmonares Límite: Humans Idioma: En Revista: Cell Rep Med Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteogenómica / Adenocarcinoma del Pulmón / Neoplasias Pulmonares Límite: Humans Idioma: En Revista: Cell Rep Med Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos