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Proteogenomic Analysis of Human Colon Cancer Reveals New Therapeutic Opportunities.
Vasaikar, Suhas; Huang, Chen; Wang, Xiaojing; Petyuk, Vladislav A; Savage, Sara R; Wen, Bo; Dou, Yongchao; Zhang, Yun; Shi, Zhiao; Arshad, Osama A; Gritsenko, Marina A; Zimmerman, Lisa J; McDermott, Jason E; Clauss, Therese R; Moore, Ronald J; Zhao, Rui; Monroe, Matthew E; Wang, Yi-Ting; Chambers, Matthew C; Slebos, Robbert J C; Lau, Ken S; Mo, Qianxing; Ding, Li; Ellis, Matthew; Thiagarajan, Mathangi; Kinsinger, Christopher R; Rodriguez, Henry; Smith, Richard D; Rodland, Karin D; Liebler, Daniel C; Liu, Tao; Zhang, Bing.
Afiliação
  • Vasaikar S; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
  • Huang C; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
  • Wang X; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
  • Petyuk VA; Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352, USA.
  • Savage SR; Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • Wen B; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
  • Dou Y; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
  • Zhang Y; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA.
  • Shi Z; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
  • Arshad OA; Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352, USA.
  • Gritsenko MA; Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352, USA.
  • Zimmerman LJ; Department of Biochemistry, Vanderbilt University, Nashville, TN 37232, USA.
  • McDermott JE; Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352, USA.
  • Clauss TR; Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352, USA.
  • Moore RJ; Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352, USA.
  • Zhao R; Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352, USA.
  • Monroe ME; Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352, USA.
  • Wang YT; Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352, USA.
  • Chambers MC; Department of Biochemistry, Vanderbilt University, Nashville, TN 37232, USA.
  • Slebos RJC; Department of Biochemistry, Vanderbilt University, Nashville, TN 37232, USA.
  • Lau KS; Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN 37232, USA.
  • Mo Q; Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
  • Ding L; The McDonnell Genome Institute, Washington University in St. Louis, Forest Park Avenue, Campus Box 8501, St. Louis, MO 63108, USA.
  • Ellis M; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
  • Thiagarajan M; Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
  • Kinsinger CR; Office of Cancer Clinical Proteomics Research, National Cancer Institute, Bethesda, MD 20892, USA.
  • Rodriguez H; Office of Cancer Clinical Proteomics Research, National Cancer Institute, Bethesda, MD 20892, USA.
  • Smith RD; Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352, USA.
  • Rodland KD; Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352, USA; Department of Cell, Developmental, and Cancer Biology, Oregon Health & Science University, Portland, OR 97221, USA. Electronic address: karin.rodland@pnnl.gov.
  • Liebler DC; Department of Biochemistry, Vanderbilt University, Nashville, TN 37232, USA. Electronic address: daniel.liebler@vanderbilt.edu.
  • Liu T; Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352, USA. Electronic address: tao.liu@pnnl.gov.
  • Zhang B; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: bi
Cell ; 177(4): 1035-1049.e19, 2019 05 02.
Article em En | MEDLINE | ID: mdl-31031003
ABSTRACT
We performed the first proteogenomic study on a prospectively collected colon cancer cohort. Comparative proteomic and phosphoproteomic analysis of paired tumor and normal adjacent tissues produced a catalog of colon cancer-associated proteins and phosphosites, including known and putative new biomarkers, drug targets, and cancer/testis antigens. Proteogenomic integration not only prioritized genomically inferred targets, such as copy-number drivers and mutation-derived neoantigens, but also yielded novel findings. Phosphoproteomics data associated Rb phosphorylation with increased proliferation and decreased apoptosis in colon cancer, which explains why this classical tumor suppressor is amplified in colon tumors and suggests a rationale for targeting Rb phosphorylation in colon cancer. Proteomics identified an association between decreased CD8 T cell infiltration and increased glycolysis in microsatellite instability-high (MSI-H) tumors, suggesting glycolysis as a potential target to overcome the resistance of MSI-H tumors to immune checkpoint blockade. Proteogenomics presents new avenues for biological discoveries and therapeutic development.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias do Colo / Proteogenômica Tipo de estudo: Observational_studies / Prognostic_studies Limite: Humans Idioma: En Revista: Cell Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias do Colo / Proteogenômica Tipo de estudo: Observational_studies / Prognostic_studies Limite: Humans Idioma: En Revista: Cell Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos