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Clinical and genomic landscape of gastric cancer with a mesenchymal phenotype

 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  ;  Jeonghoon Heo  ;  In-Sun Chu  ;  You-Jin Jang  ;  Young-Jae Mok  ;  WonKyung Jung  ;  Baek-Hui Kim  ;  Aeree Kim  ;  Jae Yong Cho  ;  Jae Yun Lim  ;  Yuki Hayashi  ;  Shumei Song  ;  Elena Elimova  ;  Jeannelyn S. Estralla  ;  Jeffrey H. Lee  ;  Manoop S. Bhutani  ;  Yiling Lu  ;  Wenbin Liu  ;  Jeeyun Lee  ;  Won Ki Kang  ;  Sung Kim  ;  Sung Hoon Noh  ;  Gordon B. Mills  ;  Seon-Young Kim  ;  Jaffer A. Ajani  ;  Ju-Seog Lee 
 Nature Communications, Vol.9(1) : 1777, 2018 
Journal Title
 Nature Communications 
Issue Date
Animals ; Antineoplastic Agents/therapeutic use ; Cell Line, Tumor ; Chemotherapy, Adjuvant ; Drug Resistance, Neoplasm ; Epithelial-Mesenchymal Transition ; Female ; Gastrointestinal Stromal Tumors/drug therapy ; Gastrointestinal Stromal Tumors/genetics* ; Gastrointestinal Stromal Tumors/metabolism ; Gastrointestinal Stromal Tumors/pathology* ; Gene Expression Regulation, Neoplastic* ; Heterografts ; Humans ; Kaplan-Meier Estimate ; Mesoderm/pathology* ; Mice, Inbred BALB C ; Microsatellite Instability ; Mutation ; Prognosis ; Proteomics ; Receptor, IGF Type 1/metabolism ; Reproducibility of Results ; Signal Transduction ; Stomach Neoplasms/drug therapy ; Stomach Neoplasms/genetics* ; Stomach Neoplasms/metabolism ; Stomach Neoplasms/pathology*
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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1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Noh, Sung Hoon(노성훈) ORCID logo https://orcid.org/0000-0003-4386-6886
Park, Ki Cheong(박기청) ORCID logo https://orcid.org/0000-0002-3435-3985
Lee, Jae Eun(이재은)
Lim, Jae Yun(임재윤)
Cheong, Jae Ho(정재호) ORCID logo https://orcid.org/0000-0002-1703-1781
Cho, Jae Yong(조재용) ORCID logo https://orcid.org/0000-0002-0926-1819
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