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Clinical and genomic landscape of gastric cancer with a mesenchymal phenotype

Author

Listed:
  • Sang Cheul Oh

    (The University of Texas MD Anderson Cancer Center
    Korea University)

  • Bo Hwa Sohn

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

  • Jae-Ho Cheong

    (Yonsei University College of Medicine)

  • Sang-Bae Kim

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

  • Jae Eun Lee

    (Yonsei University College of Medicine)

  • Ki Cheong Park

    (Yonsei University College of Medicine)

  • Sang Ho Lee

    (College of Medicine)

  • Jong-Lyul Park

    (Korea Research Institute of Bioscience and Biotechnology)

  • Yun-Yong Park

    (University of Ulsan College of Medicine)

  • Hyun-Sung Lee

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

  • Hee-Jin Jang

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

  • Eun Sung Park

    (Inha University)

  • Sang-Cheol Kim

    (National Institute of Health)

  • Jeonghoon Heo

    (College of Medicine)

  • In-Sun Chu

    (Korea Research Institute of Bioscience and Biotechnology)

  • You-Jin Jang

    (Korea University)

  • Young-Jae Mok

    (Korea University)

  • WonKyung Jung

    (Korea University)

  • Baek-Hui Kim

    (Korea University)

  • Aeree Kim

    (Korea University)

  • Jae Yong Cho

    (Yonsei University College of Medicine)

  • Jae Yun Lim

    (Yonsei University College of Medicine)

  • Yuki Hayashi

    (The University of Texas MD Anderson Cancer Center)

  • Shumei Song

    (The University of Texas MD Anderson Cancer Center)

  • Elena Elimova

    (The University of Texas MD Anderson Cancer Center)

  • Jeannelyn S. Estralla

    (The University of Texas MD Anderson Cancer Center)

  • Jeffrey H. Lee

    (The University of Texas MD Anderson Cancer Center)

  • Manoop S. Bhutani

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

  • Yiling Lu

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

  • Wenbin Liu

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

  • Jeeyun Lee

    (Division of Hematology-Oncology)

  • Won Ki Kang

    (Division of Hematology-Oncology)

  • Sung Kim

    (Samsung Medical Center)

  • Sung Hoon Noh

    (Yonsei University College of Medicine)

  • Gordon B. Mills

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

  • Seon-Young Kim

    (Korea Research Institute of Bioscience and Biotechnology)

  • Jaffer A. Ajani

    (The University of Texas MD Anderson Cancer Center)

  • Ju-Seog Lee

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

Abstract

Gastric cancer is a heterogeneous cancer, making treatment responses difficult to predict. Here we show that we identify two distinct molecular subtypes, mesenchymal phenotype (MP) and epithelial phenotype (EP), by analyzing genomic and proteomic data. Molecularly, MP subtype tumors show high genomic integrity characterized by low mutation rates and microsatellite stability, whereas EP subtype tumors show low genomic integrity. Clinically, the MP subtype is associated with markedly poor survival and resistance to standard chemotherapy, whereas the EP subtype is associated with better survival rates and sensitivity to chemotherapy. Integrative analysis shows that signaling pathways driving epithelial-to-mesenchymal transition and insulin-like growth factor 1 (IGF1)/IGF1 receptor (IGF1R) pathway are highly activated in MP subtype tumors. Importantly, MP subtype cancer cells are more sensitive to inhibition of IGF1/IGF1R pathway than EP subtype. Detailed characterization of these two subtypes could identify novel therapeutic targets and useful biomarkers for prognosis and therapy response.

Suggested Citation

  • Sang Cheul Oh & Bo Hwa Sohn & Jae-Ho Cheong & Sang-Bae Kim & Jae Eun Lee & Ki Cheong Park & Sang Ho Lee & Jong-Lyul Park & Yun-Yong Park & Hyun-Sung Lee & Hee-Jin Jang & Eun Sung Park & Sang-Cheol Kim, 2018. "Clinical and genomic landscape of gastric cancer with a mesenchymal phenotype," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04179-8
    DOI: 10.1038/s41467-018-04179-8
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    Cited by:

    1. Ke Yu & Shan Luo, 2022. "A sequential feature selection procedure for high-dimensional Cox proportional hazards model," Annals of the Institute of Statistical Mathematics, Springer;The Institute of Statistical Mathematics, vol. 74(6), pages 1109-1142, December.

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