Clinical and genomic landscape of gastric cancer with a mesenchymal phenotype
Sang Cheul OhDepartment of Internal Medicine, Guro Hospital, College of Medicine, Division of Hemato-Oncology, Korea University, Seoul, 08308, KoreaBo Hwa SohnDepartment of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USAJae‐Ho CheongDepartment of Surgery, Yonsei University College of Medicine, Seoul, 03722, KoreaSang-Bae KimDepartment of Biomedical Informatics, Center for Genome Science, National Institute of Health, Daejeon, 34141, KoreaJae Eun LeeDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USAKi Cheong ParkDepartment of Surgery, Yonsei University College of Medicine, Seoul, 03722, KoreaSang Ho LeeDepartment of Surgery, Kosin University, College of Medicine, Busan, 49267, KoreaJong‐Lyul ParkPersonalized Genomic Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 34141, KoreaYun-Yong ParkDepartment of Medicine, ASAN Institute for Life Sciences, ASAN Medical Center, University of Ulsan College of Medicine, Seoul, 05505, KoreaHyun‐Sung LeeDepartment of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USAHee-Jin JangDepartment of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USAEun Sung ParkMedical Research Institute, College of Medicine, Inha University, Incheon, 22212, KoreaSang-Cheol KimDepartment of Biomedical Informatics, Center for Genome Science, National Institute of Health, Daejeon, 34141, KoreaJeonghoon HeoDepartment of Molecular Biology and Immunology, Kosin University, College of Medicine, Busan, 49267, KoreaIn‐Sun ChuKorean Bioinformation Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 34141, KoreaYou Jin JangDepartment of Surgery, Guro Hospital, College of Medicine, Korea University, Seoul, 08308, KoreaYoung‐Jae MokDepartment of Surgery, Guro Hospital, College of Medicine, Korea University, Seoul, 08308, KoreaWonkyung JungDepartment of Surgery, Guro Hospital, College of Medicine, Korea University, Seoul, 08308, KoreaBaek‐hui KimDepartment of Pathology, Guro Hospital, College of Medicine, Korea University, Seoul, 08308, KoreaAeree KimDepartment of Pathology, Guro Hospital, College of Medicine, Korea University, Seoul, 08308, KoreaY. ChoiMedical Oncology, Yonsei University College of Medicine, Seoul, 03722, KoreaJae Yun LimMedical Oncology, Yonsei University College of Medicine, Seoul, 03722, KoreaYuki HayashiDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USAShumei SongDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USAElena ElimovaDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USAJeannelyn S. EstrallaDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USAJeffrey H. LeeDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USAManoop S. BhutaniDepartment of Gastroenterology, Hepatology, and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USAYiling LuDepartment of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USAWenbin LiuDepartment of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USAJeeyun LeeDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USAWon Ki KangDepartment of Medicine, Samsung Medical Center, Division of Hematology-Oncology, Gangnam-Gu, Seoul, 06351, KoreaSung Hoon KimDepartment of Biomedical Informatics, Center for Genome Science, National Institute of Health, Daejeon, 34141, KoreaSung Hoon NohDepartment of Surgery, Yonsei University College of Medicine, Seoul, 03722, KoreaGordon B. MillsDepartment of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USASeon‐Young KimDepartment of Biomedical Informatics, Center for Genome Science, National Institute of Health, Daejeon, 34141, KoreaJaffer A. AjaniDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USAJu‐Seog LeeDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA
2018en
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Annotatsiya
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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