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 KimJae 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

Research output: Contribution to journalArticlepeer-review

41 Citations (Scopus)

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.

Original languageEnglish
Article number1777
JournalNature communications
Volume9
Issue number1
DOIs
Publication statusPublished - 2018 Dec 1

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Fingerprint Dive into the research topics of 'Clinical and genomic landscape of gastric cancer with a mesenchymal phenotype'. Together they form a unique fingerprint.

Cite this