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Nat Commun. 2018 May 3;9(1):1777. doi: 10.1038/s41467-018-04179-8.

Clinical and genomic landscape of gastric cancer with a mesenchymal phenotype.

Author information

1
Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
2
Department of Internal Medicine, Guro Hospital, College of Medicine, Division of Hemato-Oncology, Korea University, Seoul, 08308, Korea.
3
Institute for Personalized Cancer Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
4
Department of Surgery, Yonsei University College of Medicine, Seoul, 03722, Korea.
5
Department of Surgery, Kosin University, College of Medicine, Busan, 49267, Korea.
6
Personalized Genomic Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 34141, Korea.
7
Department of Medicine, ASAN Institute for Life Sciences, ASAN Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Korea.
8
Medical Research Institute, College of Medicine, Inha University, Incheon, 22212, Korea.
9
Department of Biomedical Informatics, Center for Genome Science, National Institute of Health, Daejeon, 34141, Korea.
10
Department of Molecular Biology and Immunology, Kosin University, College of Medicine, Busan, 49267, Korea.
11
Korean Bioinformation Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 34141, Korea.
12
Department of Surgery, Guro Hospital, College of Medicine, Korea University, Seoul, 08308, Korea.
13
Department of Pathology, Guro Hospital, College of Medicine, Korea University, Seoul, 08308, Korea.
14
Medical Oncology, Yonsei University College of Medicine, Seoul, 03722, Korea.
15
Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
16
Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
17
Department of Medicine, Samsung Medical Center, Division of Hematology-Oncology, Gangnam-Gu, Seoul, 06351, Korea.
18
Department of Surgery, Samsung Medical Center, Gangnam-Gu, Seoul, 06351, Korea.
19
Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA. jlee@mdanderson.org.
20
Institute for Personalized Cancer Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA. jlee@mdanderson.org.

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.

Comment in

PMID:
29725014
PMCID:
PMC5934392
DOI:
10.1038/s41467-018-04179-8
[Indexed for MEDLINE]
Free PMC Article

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