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Body composition and lung cancer-associated cachexia in TRACERx.
Al-Sawaf, Othman; Weiss, Jakob; Skrzypski, Marcin; Lam, Jie Min; Karasaki, Takahiro; Zambrana, Francisco; Kidd, Andrew C; Frankell, Alexander M; Watkins, Thomas B K; Martínez-Ruiz, Carlos; Puttick, Clare; Black, James R M; Huebner, Ariana; Bakir, Maise Al; Sokac, Mateo; Collins, Susie; Veeriah, Selvaraju; Magno, Neil; Naceur-Lombardelli, Cristina; Prymas, Paulina; Toncheva, Antonia; Ward, Sophia; Jayanth, Nick; Salgado, Roberto; Bridge, Christopher P; Christiani, David C; Mak, Raymond H; Bay, Camden; Rosenthal, Michael; Sattar, Naveed; Welsh, Paul; Liu, Ying; Perrimon, Norbert; Popuri, Karteek; Beg, Mirza Faisal; McGranahan, Nicholas; Hackshaw, Allan; Breen, Danna M; O'Rahilly, Stephen; Birkbak, Nicolai J; Aerts, Hugo J W L; Jamal-Hanjani, Mariam; Swanton, Charles.
Afiliación
  • Al-Sawaf O; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Weiss J; Cancer Metastasis Laboratory, University College London Cancer Institute, London, UK.
  • Skrzypski M; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Lam JM; Artificial Intelligence in Medicine (AIM) Program, Mass General Brigham, Harvard Medical School, Boston, MA, USA.
  • Karasaki T; Department of Radiation Oncology, Brigham and Women's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • Zambrana F; Department of Diagnostic and Interventional Radiology, University Freiburg, Freiburg, Germany.
  • Kidd AC; Department of Oncology and Radiotherapy, Medical University of Gdansk, Gdansk, Poland.
  • Frankell AM; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Watkins TBK; Cancer Metastasis Laboratory, University College London Cancer Institute, London, UK.
  • Martínez-Ruiz C; Department of Oncology, University College London Hospitals, London, UK.
  • Puttick C; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Black JRM; Cancer Metastasis Laboratory, University College London Cancer Institute, London, UK.
  • Huebner A; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Bakir MA; Infanta Sofía University Hospital, Madrid, Spain.
  • Sokac M; Institute of Infection, Immunity & Inflammation, University of Glasgow, Glasgow, UK.
  • Collins S; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Veeriah S; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Magno N; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Naceur-Lombardelli C; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Prymas P; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Toncheva A; Cancer Genome Evolution Research Group, Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Ward S; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Jayanth N; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Salgado R; Cancer Genome Evolution Research Group, Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Bridge CP; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Christiani DC; Cancer Genome Evolution Research Group, Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Mak RH; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Bay C; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Rosenthal M; Cancer Genome Evolution Research Group, Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Sattar N; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Welsh P; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
  • Liu Y; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
  • Perrimon N; Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.
  • Popuri K; Bioinformatics Research Centre, Aarhus University, Aarhus, Denmark.
  • Beg MF; Early Clinical Development, Pfizer UK Ltd, Cambridge, UK.
  • McGranahan N; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Hackshaw A; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Breen DM; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • O'Rahilly S; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Birkbak NJ; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Aerts HJWL; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
  • Jamal-Hanjani M; Advanced Sequencing Facility, The Francis Crick Institute, London, UK.
  • Swanton C; Cancer Research UK & UCL Cancer Trials Centre, London, UK.
Nat Med ; 29(4): 846-858, 2023 04.
Article en En | MEDLINE | ID: mdl-37045997
ABSTRACT
Cancer-associated cachexia (CAC) is a major contributor to morbidity and mortality in individuals with non-small cell lung cancer. Key features of CAC include alterations in body composition and body weight. Here, we explore the association between body composition and body weight with survival and delineate potential biological processes and mediators that contribute to the development of CAC. Computed tomography-based body composition analysis of 651 individuals in the TRACERx (TRAcking non-small cell lung Cancer Evolution through therapy (Rx)) study suggested that individuals in the bottom 20th percentile of the distribution of skeletal muscle or adipose tissue area at the time of lung cancer diagnosis, had significantly shorter lung cancer-specific survival and overall survival. This finding was validated in 420 individuals in the independent Boston Lung Cancer Study. Individuals classified as having developed CAC according to one or more features at relapse encompassing loss of adipose or muscle tissue, or body mass index-adjusted weight loss were found to have distinct tumor genomic and transcriptomic profiles compared with individuals who did not develop such features. Primary non-small cell lung cancers from individuals who developed CAC were characterized by enrichment of inflammatory signaling and epithelial-mesenchymal transitional pathways, and differentially expressed genes upregulated in these tumors included cancer-testis antigen MAGEA6 and matrix metalloproteinases, such as ADAMTS3. In an exploratory proteomic analysis of circulating putative mediators of cachexia performed in a subset of 110 individuals from TRACERx, a significant association between circulating GDF15 and loss of body weight, skeletal muscle and adipose tissue was identified at relapse, supporting the potential therapeutic relevance of targeting GDF15 in the management of CAC.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Carcinoma de Pulmón de Células no Pequeñas / Neoplasias Pulmonares Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Humans / Male Idioma: En Revista: Nat Med Asunto de la revista: BIOLOGIA MOLECULAR / MEDICINA Año: 2023 Tipo del documento: Article País de afiliación: Reino Unido
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Carcinoma de Pulmón de Células no Pequeñas / Neoplasias Pulmonares Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Humans / Male Idioma: En Revista: Nat Med Asunto de la revista: BIOLOGIA MOLECULAR / MEDICINA Año: 2023 Tipo del documento: Article País de afiliación: Reino Unido