Clinical and genomic landscape of gastric cancer with a mesenchymal phenotype.
Clinical and genomic landscape of gastric cancer with a mesenchymal phenotype.
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DOI：
10.1038/s41467-018-04179-8
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发表时间：
2018-05-03
影响因子：
16.6
通讯作者：
Lee JS
中科院分区：
文献类型：
--
作者：
Oh SC;Sohn BH;Cheong JH;Kim SB;Lee JE;Park KC;Lee SH;Park JL;Park YY;Lee HS;Jang HJ;Park ES;Kim SC;Heo J;Chu IS;Jang YJ;Mok YJ;Jung W;Kim BH;Kim A;Cho JY;Lim JY;Hayashi Y;Song S;Elimova E;Estralla JS;Lee JH;Bhutani MS;Lu Y;Liu W;Lee J;Kang WK;Kim S;Noh SH;Mills GB;Kim SY;Ajani JA;Lee JS
胃癌是一种异质性癌症，治疗反应很难预测。在这里，我们通过分析基因组和蛋白质组数据，确定了两种不同的分子亚型，间充质表型(MP)和上皮表型(EP)。在分子水平上，MP亚型肿瘤表现出较高的基因组完整性，具有低突变率和微卫星稳定性的特点，而EP亚型肿瘤表现出较低的基因组完整性。临床上，MP亚型与生存率低和对标准化疗耐药有关，而EP亚型与较好的生存率和化疗敏感性有关。综合分析表明，在MP亚型肿瘤中，驱动上皮向间充质转化的信号通路和胰岛素样生长因子1(IGF1)/IGF1受体(IGF1R)通路高度激活。重要的是，MP亚型癌细胞对IGF1/IGF1R通路的抑制比EP亚型更敏感。这两个亚型的详细特征可以确定新的治疗靶点和有用的预后和治疗反应的生物标志物。异质性是影响胃癌预后和治疗的重要因素。在这里，作者揭示了两种分子亚型，间充质亚型与低存活率和化疗耐药相关，上皮表型与较好的存活率和化疗敏感性相关。
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. The prognosis and treatment of gastric cancer is complicated by heterogeneity. Here, the authors reveal two molecular subtypes, the mesenchymal subtype associated with poor survival and chemoresistance, and the epithelial phenotype associated with better survival and sensitivity to chemotherapy.
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影响因子：
15.8
作者：
Kim JH;Sohn BH;Lee HS;Kim SB;Yoo JE;Park YY;Jeong W;Lee SS;Park ES;Kaseb A;Kim BH;Kim WB;Yeon JE;Byun KS;Chu IS;Kim SS;Wang XW;Thorgeirsson SS;Luk JM;Kang KJ;Heo J;Park YN;Lee JS
通讯作者：
Lee JS
影响因子：
24.5
作者：
Jawhari, A;Farthing, M;Pignatelli, M
通讯作者：
Pignatelli, M
影响因子：
64.8
作者：
Cancer Genome Atlas Research Network;Analysis Working Group: Asan University;BC Cancer Agency;Brigham and Women’s Hospital;Broad Institute;Brown University;Case Western Reserve University;Dana-Farber Cancer Institute;Duke University;Greater Poland Cancer Centre;Harvard Medical School;Institute for Systems Biology;KU Leuven;Mayo Clinic;Memorial Sloan Kettering Cancer Center;National Cancer Institute;Nationwide Children’s Hospital;Stanford University;University of Alabama;University of Michigan;University of North Carolina;University of Pittsburgh;University of Rochester;University of Southern California;University of Texas MD Anderson Cancer Center;University of Washington;Van Andel Research Institute;Vanderbilt University;Washington University;Genome Sequencing Center: Broad Institute;Washington University in St. Louis;Genome Characterization Centers: BC Cancer Agency;Broad Institute;Harvard Medical School;Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University;University of North Carolina;University of Southern California Epigenome Center;University of Texas MD Anderson Cancer Center;Van Andel Research Institute;Genome Data Analysis Centers: Broad Institute;Brown University:;Harvard Medical School;Institute for Systems Biology;Memorial Sloan Kettering Cancer Center;University of California Santa Cruz;University of Texas MD Anderson Cancer Center;Biospecimen Core Resource: International Genomics Consortium;Research Institute at Nationwide Children’s Hospital;Tissue Source Sites: Analytic Biologic Services;Asan Medical Center;Asterand Bioscience;Barretos Cancer Hospital;BioreclamationIVT;Botkin Municipal Clinic;Chonnam National University Medical School;Christiana Care Health System;Cureline;Duke University;Emory University;Erasmus University;Indiana University School of Medicine;Institute of Oncology of Moldova;International Genomics Consortium;Invidumed;Israelitisches Krankenhaus Hamburg;Keimyung University School of Medicine;Memorial Sloan Kettering Cancer Center;National Cancer Center Goyang;Ontario Tumour Bank;Peter MacCallum Cancer Centre;Pusan National University Medical School;Ribeirão Preto Medical School;St. Joseph’s Hospital &Medical Center;St. Petersburg Academic University;Tayside Tissue Bank;University of Dundee;University of Kansas Medical Center;University of Michigan;University of North Carolina at Chapel Hill;University of Pittsburgh School of Medicine;University of Texas MD Anderson Cancer Center;Disease Working Group: Duke University;Memorial Sloan Kettering Cancer Center;National Cancer Institute;University of Texas MD Anderson Cancer Center;Yonsei University College of Medicine;Data Coordination Center: CSRA Inc.;Project Team: National Institutes of Health
通讯作者：
Project Team: National Institutes of Health
影响因子：
64.5
作者：
Cancer Genome Atlas Research Network. Electronic address: wheeler@bcm.edu;Cancer Genome Atlas Research Network
通讯作者：
Cancer Genome Atlas Research Network
影响因子：
4.8
作者：
Bailey, Kelly M.;Liu, Jun
通讯作者：
Liu, Jun