دورية أكاديمية
Body composition and lung cancer-associated cachexia in TRACERx.
| العنوان: | Body composition and lung cancer-associated cachexia in TRACERx. |
|---|---|
| المؤلفون: | Al-Sawaf O; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.; Cancer Metastasis Laboratory, University College London Cancer Institute, London, UK.; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK., Weiss J; Artificial Intelligence in Medicine (AIM) Program, Mass General Brigham, Harvard Medical School, Boston, MA, USA.; Department of Radiation Oncology, Brigham and Women's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.; Department of Diagnostic and Interventional Radiology, University Freiburg, Freiburg, Germany., Skrzypski M; Department of Oncology and Radiotherapy, Medical University of Gdańsk, Gdańsk, Poland., Lam JM; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.; Cancer Metastasis Laboratory, University College London Cancer Institute, London, UK.; Department of Oncology, University College London Hospitals, London, UK., Karasaki T; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.; Cancer Metastasis Laboratory, University College London Cancer Institute, London, UK.; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK., Zambrana F; Infanta Sofía University Hospital, Madrid, Spain., Kidd AC; Institute of Infection, Immunity & Inflammation, University of Glasgow, Glasgow, UK., Frankell AM; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK., Watkins TBK; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK., Martínez-Ruiz C; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.; Cancer Genome Evolution Research Group, Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK., Puttick C; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.; Cancer Genome Evolution Research Group, Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK., Black JRM; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.; Cancer Genome Evolution Research Group, Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK., Huebner A; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.; Cancer Genome Evolution Research Group, Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK., Bakir MA; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK., Sokač M; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.; Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.; Bioinformatics Research Centre, Aarhus University, Aarhus, Denmark., Collins S; Early Clinical Development, Pfizer UK Ltd, Cambridge, UK., Veeriah S; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK., Magno N; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK., Naceur-Lombardelli C; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK., Prymas P; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK., Toncheva A; 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.; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.; Advanced Sequencing Facility, The Francis Crick Institute, London, UK., Jayanth N; Cancer Research UK & UCL Cancer Trials Centre, London, UK., Salgado R; Department of Pathology, ZAS Hospitals, Antwerp, Belgium.; Division of Research, Peter MacCallum Cancer Centre, Melbourne, Australia., Bridge CP; MGH & BWH Center for Clinical Data Science, Boston, MA, USA., Christiani DC; Department of Medicine, Massachusetts General Hospital/Harvard Medicine School, and Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA., Mak RH; Artificial Intelligence in Medicine (AIM) Program, Mass General Brigham, Harvard Medical School, Boston, MA, USA.; Department of Radiation Oncology, Brigham and Women's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA., Bay C; Department of Radiology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, and Harvard Medical School, Boston, MA, USA., Rosenthal M; Department of Radiology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, and Harvard Medical School, Boston, MA, USA., Sattar N; School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK., Welsh P; School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK., Liu Y; Department of Genetics, Harvard Medical School, Boston, USA.; Howard Hughes Medical Institute, Harvard Medical School, Boston, USA., Perrimon N; Department of Genetics, Harvard Medical School, Boston, USA.; Howard Hughes Medical Institute, Harvard Medical School, Boston, USA., Popuri K; Department of Computer Science, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador, Burnaby, Canada., Beg MF; School of Engineering Science, Simon Fraser University, Burnaby, British Colombia, Canada., McGranahan N; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.; Cancer Genome Evolution Research Group, Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK., Hackshaw A; Cancer Research UK & UCL Cancer Trials Centre, London, UK., Breen DM; Internal Medicine Research Unit, Pfizer, Cambridge, MA, USA., O'Rahilly S; Wellcome Trust-MRC Institute of Metabolic Science and NIHR Cambridge Biomedical Research Centre, University of Cambridge, Cambridge, UK., Birkbak NJ; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.; Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.; Bioinformatics Research Centre, Aarhus University, Aarhus, Denmark., Aerts HJWL; Artificial Intelligence in Medicine (AIM) Program, Mass General Brigham, Harvard Medical School, Boston, MA, USA.; Department of Radiation Oncology, Brigham and Women's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.; Radiology and Nuclear Medicine, CARIM & GROW, Maastricht University, Maastricht, The Netherlands., Jamal-Hanjani M; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK. m.jamal-hanjani@ucl.ac.uk.; Cancer Metastasis Laboratory, University College London Cancer Institute, London, UK. m.jamal-hanjani@ucl.ac.uk.; Department of Oncology, University College London Hospitals, London, UK. m.jamal-hanjani@ucl.ac.uk., Swanton C; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK. Charles.swanton@crick.ac.uk.; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK. Charles.swanton@crick.ac.uk.; Department of Oncology, University College London Hospitals, London, UK. Charles.swanton@crick.ac.uk. |
| مؤلفون مشاركون: | TRACERx Consortium |
| المصدر: | Nature medicine [Nat Med] 2023 Apr; Vol. 29 (4), pp. 846-858. Date of Electronic Publication: 2023 Apr 12. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Nature Publishing Company Country of Publication: United States NLM ID: 9502015 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1546-170X (Electronic) Linking ISSN: 10788956 NLM ISO Abbreviation: Nat Med Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: New York Ny : Nature Publishing Company Original Publication: New York, NY : Nature Pub. Co., [1995- |
| مواضيع طبية MeSH: | Lung Neoplasms*/pathology , Carcinoma, Non-Small-Cell Lung*/pathology, Male ; Humans ; Cachexia/complications ; Proteomics ; Neoplasm Recurrence, Local/pathology ; Body Composition ; Body Weight ; Muscle, Skeletal/metabolism ; Antigens, Neoplasm/metabolism ; Neoplasm Proteins |
| مستخلص: | 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. (© 2023. The Author(s) under exclusive license to Springer Nature America, Inc.) |
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| معلومات مُعتمدة: | R35 CA197449 United States CA NCI NIH HHS; CTRNBC-2022/100001 United Kingdom CRUK_ Cancer Research UK; U19 CA203654 United States CA NCI NIH HHS; MR/V033077/1 United Kingdom MRC_ Medical Research Council; CC2041 United Kingdom MRC_ Medical Research Council; CC2041 United Kingdom CRUK_ Cancer Research UK; 25349 United Kingdom CRUK_ Cancer Research UK; 21999 United Kingdom CRUK_ Cancer Research UK; FC001169 United Kingdom ARC_ Arthritis Research UK; CC2041 United Kingdom WT_ Wellcome Trust; 24956 United Kingdom CRUK_ Cancer Research UK; United Kingdom WT_ Wellcome Trust; 17786 United Kingdom CRUK_ Cancer Research UK; 29569 United Kingdom CRUK_ Cancer Research UK; 30025 United Kingdom CRUK_ Cancer Research UK |
| فهرسة مساهمة: | Investigator: TBK Watkins; NJ Birkbak; HJ Aerts; JF Lester; A Bajaj; A Nakas; A Sodha-Ramdeen; K Ang; M Tufail; MF Chowdhry; M Scotland; R Boyles; S Rathinam; C Wilson; D Marrone; S Dulloo; DA Fennell; G Matharu; JA Shaw; J Riley; L Primrose; E Boleti; H Cheyne; M Khalil; S Richardson; T Cruickshank; G Price; KM Kerr; S Benafif; K Gilbert; B Naidu; AJ Patel; A Osman; C Lacson; G Langman; H Shackleford; M Djearaman; S Kadiri; G Middleton; A Leek; JD Hodgkinson; N Totten; A Montero; E Smith; E Fontaine; F Granato; H Doran; J Novasio; K Rammohan; L Joseph; P Bishop; R Shah; S Moss; V Joshi; P Crosbie; F Gomes; K Brown; M Carter; A Chaturvedi; L Priest; P Oliveira; CR Lindsay; FH Blackhall; MG Krebs; Y Summers; A Clipson; J Tugwood; A Kerr; DG Rothwell; E Kilgour; C Dive; RF Schwarz; TL Kaufmann; GA Wilson; R Rosenthal; P Van Loo; Z Szallasi; J Kisistok; M Sokac; M Diossy; J Demeulemeester; A Bunkum; A Stewart; A Magness; A Rowan; A Karamani; B Chain; BB Campbell; C Castignani; C Bailey; C Abbosh; CE Weeden; C Lee; C Richard; CT Hiley; DA Moore; DR Pearce; D Karagianni; D Biswas; D Levi; E Hoxha; EL Cadieux; EL Lim; E Colliver; E Nye; E Grönroos; F Gálvez-Cancino; F Athanasopoulou; F Gimeno-Valiente; G Kassiotis; G Stavrou; G Mastrokalos; H Zhai; HL Lowe; IG Matos; J Goldman; JL Reading; J Herrero; JK Rane; J Nicod; JA Hartley; KS Peggs; KSS Enfield; K Selvaraju; K Thol; K Litchfield; KW Ng; K Chen; K Dijkstra; K Grigoriadis; K Thakkar; L Ensell; M Shah; MV Duran; M Litovchenko; MW Sunderland; MS Hill; M Dietzen; M Leung; M Escudero; M Angelova; M Tanić; M Sivakumar; N Kanu; O Chervova; O Lucas; O Pich; P Hobson; P Pawlik; RK Stone; R Bentham; RE Hynds; R Vendramin; S Saghafinia; S López; S Gamble; SKA Ung; SA Quezada; S Vanloo; S Zaccaria; S Hessey; S Boeing; S Beck; SK Bola; T Denner; T Marafioti; TP Mourikis; V Spanswick; V Barbè; WT Lu; W Hill; WK Liu; Y Wu; Y Naito; Z Ramsden; C Veiga; G Royle; CA Collins-Fekete; F Fraioli; P Ashford; T Clark; MD Forster; SM Lee; E Borg; M Falzon; D Papadatos-Pastos; J Wilson; T Ahmad; AJ Procter; A Ahmed; MN Taylor; A Nair; D Lawrence; D Patrini; N Navani; RM Thakrar; SM Janes; EM Hoogenboom; F Monk; JW Holding; J Choudhary; K Bhakhri; M Scarci; M Hayward; N Panagiotopoulos; P Gorman; R Khiroya; RC Stephens; YNS Wong; S Bandula; A Sharp; S Smith; N Gower; HK Dhanda; K Chan; C Pilotti; R Leslie; A Grapa; H Zhang; K AbdulJabbar; X Pan; Y Yuan; D Chuter; M MacKenzie; S Chee; A Alzetani; J Cave; L Scarlett; J Richards; P Ingram; S Austin; E Lim; P De Sousa; S Jordan; A Rice; H Raubenheimer; H Bhayani; L Ambrose; A Devaraj; H Chavan; S Begum; SI Buderi; D Kaniu; M Malima; S Booth; AG Nicholson; N Fernandes; P Shah; C Proli; M Hewish; S Danson; MJ Shackcloth; L Robinson; P Russell; KG Blyth; C Dick; J Le Quesne; A Kirk; M Asif; R Bilancia; N Kostoulas; M Thomas |
| المشرفين على المادة: | 0 (MAGEA6 protein, human) 0 (Antigens, Neoplasm) 0 (Neoplasm Proteins) |
| تواريخ الأحداث: | Date Created: 20230412 Date Completed: 20230421 Latest Revision: 20240917 |
| رمز التحديث: | 20240917 |
| مُعرف محوري في PubMed: | PMC7614477 |
| DOI: | 10.1038/s41591-023-02232-8 |
| PMID: | 37045997 |
| قاعدة البيانات: | MEDLINE |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 1546-170X |
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| DOI: | 10.1038/s41591-023-02232-8 |