Clinical and genomic landscape of gastric cancer with a mesenchymal phenotype

Sang Cheul Oh(The University of Texas MD Anderson Cancer Center), Bo Hwa Sohn(The University of Texas MD Anderson Cancer Center), Jae‐Ho Cheong(Yonsei University), Sang-Bae Kim(The University of Texas MD Anderson Cancer Center), Jae Eun Lee(The University of Texas MD Anderson Cancer Center), Ki Cheong Park(Yonsei University), Sang Ho Lee(Kosin University), Jong‐Lyul Park(Korea Research Institute of Bioscience and Biotechnology), Yun-Yong Park(Ulsan College), Hyun‐Sung Lee(The University of Texas MD Anderson Cancer Center), Hee-Jin Jang(The University of Texas MD Anderson Cancer Center), Eun Sung Park(Inha University), Sang-Cheol Kim(The University of Texas MD Anderson Cancer Center), Jeonghoon Heo(Kosin University), 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), Y. Choi(Yonsei University), Jae Yun Lim(Yonsei University), 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), Yiling Lu(The University of Texas MD Anderson Cancer Center), Wenbin Liu(The University of Texas MD Anderson Cancer Center), Jeeyun Lee(The University of Texas MD Anderson Cancer Center), Won Ki Kang(Samsung Medical Center), Sung Hoon Kim(The University of Texas MD Anderson Cancer Center), Sung Hoon Noh(Yonsei University), Gordon B. Mills(The University of Texas MD Anderson Cancer Center), Seon‐Young Kim(The University of Texas MD Anderson Cancer Center), Jaffer A. Ajani(The University of Texas MD Anderson Cancer Center), Ju‐Seog Lee(The University of Texas MD Anderson Cancer Center)
Nature Communications
April 27, 2018
10.1038/s41467-018-04179-8
Cited by 462Open Access
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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.

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