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Proteogenomic characterization of small cell lung cancer identifies biological insights and subtype-specific therapeutic strategies.
Liu, Qian; Zhang, Jing; Guo, Chenchen; Wang, Mengcheng; Wang, Chenfei; Yan, Yilv; Sun, Liangdong; Wang, Di; Zhang, Lele; Yu, Huansha; Hou, Likun; Wu, Chunyan; Zhu, Yuming; Jiang, Gening; Zhu, Hongwen; Zhou, Yanting; Fang, Shanhua; Zhang, Tengfei; Hu, Liang; Li, Junqiang; Liu, Yansheng; Zhang, Hui; Zhang, Bing; Ding, Li; Robles, Ana I; Rodriguez, Henry; Gao, Daming; Ji, Hongbin; Zhou, Hu; Zhang, Peng.
Afiliação
  • Liu Q; Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, China; Department of Analytical Chemistry, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
  • Zhang J; Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, China.
  • Guo C; State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, CAS Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, China.
  • Wang M; State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, CAS Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, China.
  • Wang C; Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Department of Orthopedics, Tongji Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China; Frontier Science Center for Stem Cells, School of Life Sciences and Technolo
  • Yan Y; Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, China.
  • Sun L; Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, China.
  • Wang D; Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, China.
  • Zhang L; Central Laboratory, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, China.
  • Yu H; Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, China.
  • Hou L; Department of Pathology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, China.
  • Wu C; Department of Pathology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, China.
  • Zhu Y; Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, China.
  • Jiang G; Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, China.
  • Zhu H; Department of Analytical Chemistry, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
  • Zhou Y; Department of Analytical Chemistry, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
  • Fang S; Department of Analytical Chemistry, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
  • Zhang T; State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, CAS Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, China.
  • Hu L; State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, CAS Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, China.
  • Li J; D1 Medical Technology, Shanghai 201800, China.
  • Liu Y; Cancer Biology Institute, Yale University School of Medicine, West Haven, CT 06516, USA.
  • Zhang H; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  • Zhang B; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA.
  • Ding L; Department of Medicine, McDonnell Genome Institute, Washington University, St. Louis, MO 63108, USA.
  • Robles AI; Office of Cancer Clinical Proteomics Research, National Cancer Institute, National Institutes of Health, Rockville, MD 20850, USA.
  • Rodriguez H; Office of Cancer Clinical Proteomics Research, National Cancer Institute, National Institutes of Health, Rockville, MD 20850, USA.
  • Gao D; State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, CAS Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, China; Key Laboratory of Systems Health Scie
  • Ji H; State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, CAS Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, China; Key Laboratory of Systems Health Scie
  • Zhou H; Department of Analytical Chemistry, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, Beijing 100049, China; School of Pharmaceutical Science and Technology, Hangzhou Institute
  • Zhang P; Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, China. Electronic address: zhangpeng1121@tongji.edu.cn.
Cell ; 187(1): 184-203.e28, 2024 01 04.
Article em En | MEDLINE | ID: mdl-38181741
ABSTRACT
We performed comprehensive proteogenomic characterization of small cell lung cancer (SCLC) using paired tumors and adjacent lung tissues from 112 treatment-naive patients who underwent surgical resection. Integrated multi-omics analysis illustrated cancer biology downstream of genetic aberrations and highlighted oncogenic roles of FAT1 mutation, RB1 deletion, and chromosome 5q loss. Two prognostic biomarkers, HMGB3 and CASP10, were identified. Overexpression of HMGB3 promoted SCLC cell migration via transcriptional regulation of cell junction-related genes. Immune landscape characterization revealed an association between ZFHX3 mutation and high immune infiltration and underscored a potential immunosuppressive role of elevated DNA damage response activity via inhibition of the cGAS-STING pathway. Multi-omics clustering identified four subtypes with subtype-specific therapeutic vulnerabilities. Cell line and patient-derived xenograft-based drug tests validated the specific therapeutic responses predicted by multi-omics subtyping. This study provides a valuable resource as well as insights to better understand SCLC biology and improve clinical practice.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Carcinoma de Pequenas Células do Pulmão / Proteogenômica / Neoplasias Pulmonares Limite: Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Carcinoma de Pequenas Células do Pulmão / Proteogenômica / Neoplasias Pulmonares Limite: Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article