한빛사 논문
Sang Cheul Oh1,2, Bo Hwa Sohn1,3, Jae-Ho Cheong4, Sang-Bae Kim1,3, Jae Eun Lee4, Ki Cheong Park4, Sang Ho Lee5, Jong-Lyul Park6, Yun-Yong Park7, Hyun-Sung Lee1,3, Hee-Jin Jang1,3, Eun Sung Park8, Sang-Cheol Kim9, Jeonghoon Heo10, In-Sun Chu11, You-Jin Jang12, Young-Jae Mok12, WonKyung Jung12, Baek-Hui Kim13, Aeree Kim13, Jae Yong Cho14, Jae Yun Lim14, Yuki Hayashi15, Shumei Song15, Elena Elimova15, Jeannelyn S. Estralla15, Jeffrey H. Lee15, Manoop S. Bhutani15,16, Yiling Lu1,3, Wenbin Liu1,3, Jeeyun Lee17, Won Ki Kang17, Sung Kim18, Sung Hoon Noh4, Gordon B. Mills1,3, Seon-Young Kim 6, Jaffer A. Ajani15 & Ju-Seog Lee1,3,*
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.
These authors contributed equally: Sang Cheul Oh, Bo Hwa Sohn, Jae-Ho Cheong, Sang-Bae Kim. *Correspondence and requests for materials should be addressed to J.-S.L.
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.
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