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Integrative network analysis of early-stage lung adenocarcinoma identifies aurora kinase inhibition as interceptor of invasion and progression.

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机构： [1]Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA. [2]Icahn Institute for Data Science and Genomic Technology, New York, NY, USA. [3]Sema4, Stamford, CT, USA. [4]Division of Pulmonary, Critical Care and Sleep Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA. [5]Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. [6]Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai, China. [7]Department of Cardiothoracic Surgery, Weill Cornell Medicine-New York Presbyterian Hospital, New York, NY, USA. [8]School of Medicine, St. George’s University, West Indies, Grenada. [9]Vileck Institute of Graduate Biomedical Sciences, New York University School of Medicine, New York, NY, USA. [10]Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan. [11]Department of Respiratory Medicine, Kitasato University School of Medicine, Sagamihara, Japan. [12]Department of Thoracic Surgery, The Second Affiliated Hospital of Medical School, Xi’an Jiaotong University, Xi’an, Shaanxi, China [13]Key Laboratory of Birth Defects and Related Diseases of Women And Children of MOE, State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China. [14]Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA. [15]Department of Pathology, Weill Cornell Medicine, New York, NY, USA.

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Here we focus on the molecular characterization of clinically significant histological subtypes of early-stage lung adenocarcinoma (esLUAD), which is the most common histological subtype of lung cancer. Within lung adenocarcinoma, histology is heterogeneous and associated with tumor invasion and diverse clinical outcomes. We present a gene signature distinguishing invasive and non-invasive tumors among esLUAD. Using the gene signatures, we estimate an Invasiveness Score that is strongly associated with survival of esLUAD patients in multiple independent cohorts and with the invasiveness phenotype in lung cancer cell lines. Regulatory network analysis identifies aurora kinase as one of master regulators of the gene signature and the perturbation of aurora kinases in vitro and in a murine model of invasive lung adenocarcinoma reduces tumor invasion. Our study reveals aurora kinases as a therapeutic target for treatment of early-stage invasive lung adenocarcinoma.© 2022. The Author(s).

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小类 | 1 区综合性期刊

第一作者：

第一作者机构： [1]Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA. [2]Icahn Institute for Data Science and Genomic Technology, New York, NY, USA. [3]Sema4, Stamford, CT, USA.

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通讯作者：

通讯机构： [1]Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA. [2]Icahn Institute for Data Science and Genomic Technology, New York, NY, USA. [3]Sema4, Stamford, CT, USA. [4]Division of Pulmonary, Critical Care and Sleep Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA. [5]Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

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