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Proteogenomic landscape of squamous cell lung cancer

Author

Listed:
  • Paul A. Stewart

    (H. Lee Moffitt Cancer Center and Research Institute
    H. Lee Moffitt Cancer Center and Research Institute)

  • Eric A. Welsh

    (H. Lee Moffitt Cancer Center and Research Institute)

  • Robbert J. C. Slebos

    (H. Lee Moffitt Cancer Center and Research Institute)

  • Bin Fang

    (H. Lee Moffitt Cancer Center and Research Institute)

  • Victoria Izumi

    (H. Lee Moffitt Cancer Center and Research Institute)

  • Matthew Chambers

    (H. Lee Moffitt Cancer Center and Research Institute)

  • Guolin Zhang

    (H. Lee Moffitt Cancer Center and Research Institute)

  • Ling Cen

    (H. Lee Moffitt Cancer Center and Research Institute)

  • Fredrik Pettersson

    (H. Lee Moffitt Cancer Center and Research Institute)

  • Yonghong Zhang

    (H. Lee Moffitt Cancer Center and Research Institute)

  • Zhihua Chen

    (H. Lee Moffitt Cancer Center and Research Institute)

  • Chia-Ho Cheng

    (H. Lee Moffitt Cancer Center and Research Institute)

  • Ram Thapa

    (H. Lee Moffitt Cancer Center and Research Institute)

  • Zachary Thompson

    (H. Lee Moffitt Cancer Center and Research Institute)

  • Katherine M. Fellows

    (H. Lee Moffitt Cancer Center and Research Institute)

  • Jewel M. Francis

    (H. Lee Moffitt Cancer Center and Research Institute)

  • James J. Saller

    (H. Lee Moffitt Cancer Center and Research Institute)

  • Tania Mesa

    (H. Lee Moffitt Cancer Center and Research Institute)

  • Chaomei Zhang

    (H. Lee Moffitt Cancer Center and Research Institute)

  • Sean Yoder

    (H. Lee Moffitt Cancer Center and Research Institute)

  • Gina M. DeNicola

    (H. Lee Moffitt Cancer Center and Research Institute)

  • Amer A. Beg

    (H. Lee Moffitt Cancer Center and Research Institute)

  • Theresa A. Boyle

    (H. Lee Moffitt Cancer Center and Research Institute)

  • Jamie K. Teer

    (H. Lee Moffitt Cancer Center and Research Institute)

  • Yian Ann Chen

    (H. Lee Moffitt Cancer Center and Research Institute)

  • John M. Koomen

    (H. Lee Moffitt Cancer Center and Research Institute)

  • Steven A. Eschrich

    (H. Lee Moffitt Cancer Center and Research Institute)

  • Eric B. Haura

    (H. Lee Moffitt Cancer Center and Research Institute)

Abstract

How genomic and transcriptomic alterations affect the functional proteome in lung cancer is not fully understood. Here, we integrate DNA copy number, somatic mutations, RNA-sequencing, and expression proteomics in a cohort of 108 squamous cell lung cancer (SCC) patients. We identify three proteomic subtypes, two of which (Inflamed, Redox) comprise 87% of tumors. The Inflamed subtype is enriched with neutrophils, B-cells, and monocytes and expresses more PD-1. Redox tumours are enriched for oxidation-reduction and glutathione pathways and harbor more NFE2L2/KEAP1 alterations and copy gain in the 3q2 locus. Proteomic subtypes are not associated with patient survival. However, B-cell-rich tertiary lymph node structures, more common in Inflamed, are associated with better survival. We identify metabolic vulnerabilities (TP63, PSAT1, and TFRC) in Redox. Our work provides a powerful resource for lung SCC biology and suggests therapeutic opportunities based on redox metabolism and immune cell infiltrates.

Suggested Citation

  • Paul A. Stewart & Eric A. Welsh & Robbert J. C. Slebos & Bin Fang & Victoria Izumi & Matthew Chambers & Guolin Zhang & Ling Cen & Fredrik Pettersson & Yonghong Zhang & Zhihua Chen & Chia-Ho Cheng & Ra, 2019. "Proteogenomic landscape of squamous cell lung cancer," Nature Communications, Nature, vol. 10(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11452-x
    DOI: 10.1038/s41467-019-11452-x
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    Cited by:

    1. Jennifer G. Abelin & Erik J. Bergstrom & Keith D. Rivera & Hannah B. Taylor & Susan Klaeger & Charles Xu & Eva K. Verzani & C. Jackson White & Hilina B. Woldemichael & Maya Virshup & Meagan E. Olive &, 2023. "Workflow enabling deepscale immunopeptidome, proteome, ubiquitylome, phosphoproteome, and acetylome analyses of sample-limited tissues," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    2. Poon, Charlotte & Haderi, Artes & Roediger, Alexander & Yuan, Megan, 2022. "Should we screen for lung cancer? A 10-country analysis identifying key decision-making factors," Health Policy, Elsevier, vol. 126(9), pages 879-888.
    3. Shideh Mirhadi & Shirley Tam & Quan Li & Nadeem Moghal & Nhu-An Pham & Jiefei Tong & Brian J. Golbourn & Jonathan R. Krieger & Paul Taylor & Ming Li & Jessica Weiss & Sebastiao N. Martins-Filho & Vibh, 2022. "Integrative analysis of non-small cell lung cancer patient-derived xenografts identifies distinct proteotypes associated with patient outcomes," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    4. Shengli Li & Li Yuan & Zhi-Yuan Xu & Jing-Li Xu & Gui-Ping Chen & Xiaoqing Guan & Guang-Zhao Pan & Can Hu & Jinyun Dong & Yi-An Du & Li-Tao Yang & Mao-Wei Ni & Rui-Bin Jiang & Xiu Zhu & Hang Lv & Han-, 2023. "Integrative proteomic characterization of adenocarcinoma of esophagogastric junction," Nature Communications, Nature, vol. 14(1), pages 1-19, December.

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