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.

Details

Title
Clinical and genomic landscape of gastric cancer with a mesenchymal phenotype
Author
Oh, Sang Cheul 1 ; Sohn, Bo Hwa 2 ; Jae-Ho, Cheong 3 ; Sang-Bae, Kim 2 ; Lee, Jae Eun 3 ; Park, Ki Cheong 3 ; Sang Ho Lee 4 ; Park, Jong-Lyul 5 ; Yun-Yong, Park 6 ; Hyun-Sung, Lee 2   VIAFID ORCID Logo  ; Hee-Jin, Jang 2   VIAFID ORCID Logo  ; Eun Sung Park 7 ; Sang-Cheol, Kim 8 ; Heo, Jeonghoon 9 ; Chu, In-Sun 10 ; You-Jin, Jang 11 ; Young-Jae Mok 11 ; Jung, WonKyung 11 ; Baek-Hui, Kim 12 ; Kim, Aeree 12 ; Jae Yong Cho 13 ; Jae Yun Lim 13 ; Hayashi, Yuki 14 ; Song, Shumei 14 ; Elimova, Elena 14 ; Estralla, Jeannelyn S 14 ; Lee, Jeffrey H 14 ; Bhutani, Manoop S 15 ; Lu, Yiling 2 ; Liu, Wenbin 2 ; Lee, Jeeyun 16 ; Kang, Won Ki 16 ; Kim, Sung 17 ; Noh, Sung Hoon 3 ; Mills, Gordon B 2 ; Seon-Young, Kim 5   VIAFID ORCID Logo  ; Ajani, Jaffer A 14 ; Lee, Ju-Seog 2   VIAFID ORCID Logo 

1  Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Internal Medicine, Guro Hospital, College of Medicine, Division of Hemato-Oncology, Korea University, Seoul, Korea 
2  Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Institute for Personalized Cancer Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 
3  Department of Surgery, Yonsei University College of Medicine, Seoul, Korea 
4  Department of Surgery, Kosin University, College of Medicine, Busan, Korea 
5  Personalized Genomic Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea 
6  Department of Medicine, ASAN Institute for Life Sciences, ASAN Medical Center, University of Ulsan College of Medicine, Seoul, Korea 
7  Medical Research Institute, College of Medicine, Inha University, Incheon, Korea 
8  Department of Biomedical Informatics, Center for Genome Science, National Institute of Health, Daejeon, Korea 
9  Department of Molecular Biology and Immunology, Kosin University, College of Medicine, Busan, Korea 
10  Korean Bioinformation Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea 
11  Department of Surgery, Guro Hospital, College of Medicine, Korea University, Seoul, Korea 
12  Department of Pathology, Guro Hospital, College of Medicine, Korea University, Seoul, Korea 
13  Medical Oncology, Yonsei University College of Medicine, Seoul, Korea 
14  Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 
15  Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 
16  Department of Medicine, Samsung Medical Center, Division of Hematology-Oncology, Gangnam-Gu, Seoul, Korea 
17  Department of Surgery, Samsung Medical Center, Gangnam-Gu, Seoul, Korea 
Pages
1-14
Publication year
2018
Publication date
May 2018
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-018-04179-8
ProQuest document ID
2034273858
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.