Preliminary results from the EMoLung clinical study showing early lung cancer detection by the LC score.

Biomarker Diagnostic Exhaled breath condensate GATA6 Lung cancer NKX2-1

Journal

Discover. Oncology
ISSN: 2730-6011
Titre abrégé: Discov Oncol
Pays: United States
ID NLM: 101775142

Informations de publication

Date de publication:
03 Oct 2023
Historique:
received: 16 07 2023
accepted: 22 09 2023
medline: 3 10 2023
pubmed: 3 10 2023
entrez: 3 10 2023
Statut: epublish

Résumé

Lung cancer (LC) causes more deaths worldwide than any other cancer type. Despite advances in therapeutic strategies, the fatality rate of LC cases remains high (95%) since the majority of patients are diagnosed at late stages when patient prognosis is poor. Analysis of the International Association for the Study of Lung Cancer (IASLC) database indicates that early diagnosis is significantly associated with favorable outcome. However, since symptoms of LC at early stages are unspecific and resemble those of benign pathologies, current diagnostic approaches are mostly initiated at advanced LC stages. We developed a LC diagnosis test based on the analysis of distinct RNA isoforms expressed from the GATA6 and NKX2-1 gene loci, which are detected in exhaled breath condensates (EBCs). Levels of these transcript isoforms in EBCs were combined to calculate a diagnostic score (the LC score). In the present study, we aimed to confirm the applicability of the LC score for the diagnosis of early stage LC under clinical settings. Thus, we evaluated EBCs from patients with early stage, resectable non-small cell lung cancer (NSCLC), who were prospectively enrolled in the EMoLung study at three sites in Germany. LC score-based classification of EBCs confirmed its performance under clinical conditions, achieving a sensitivity of 95.7%, 91.3% and 84.6% for LC detection at stages I, II and III, respectively. The LC score is an accurate and non-invasive option for early LC diagnosis and a valuable complement to LC screening procedures based on computed tomography.

Sections du résumé

BACKGROUND BACKGROUND
Lung cancer (LC) causes more deaths worldwide than any other cancer type. Despite advances in therapeutic strategies, the fatality rate of LC cases remains high (95%) since the majority of patients are diagnosed at late stages when patient prognosis is poor. Analysis of the International Association for the Study of Lung Cancer (IASLC) database indicates that early diagnosis is significantly associated with favorable outcome. However, since symptoms of LC at early stages are unspecific and resemble those of benign pathologies, current diagnostic approaches are mostly initiated at advanced LC stages.
METHODS METHODS
We developed a LC diagnosis test based on the analysis of distinct RNA isoforms expressed from the GATA6 and NKX2-1 gene loci, which are detected in exhaled breath condensates (EBCs). Levels of these transcript isoforms in EBCs were combined to calculate a diagnostic score (the LC score). In the present study, we aimed to confirm the applicability of the LC score for the diagnosis of early stage LC under clinical settings. Thus, we evaluated EBCs from patients with early stage, resectable non-small cell lung cancer (NSCLC), who were prospectively enrolled in the EMoLung study at three sites in Germany.
RESULTS RESULTS
LC score-based classification of EBCs confirmed its performance under clinical conditions, achieving a sensitivity of 95.7%, 91.3% and 84.6% for LC detection at stages I, II and III, respectively.
CONCLUSIONS CONCLUSIONS
The LC score is an accurate and non-invasive option for early LC diagnosis and a valuable complement to LC screening procedures based on computed tomography.

Identifiants

pubmed: 37787775
doi: 10.1007/s12672-023-00799-9
pii: 10.1007/s12672-023-00799-9
pmc: PMC10547665
doi:

Types de publication

Journal Article

Langues

eng

Pagination

181

Subventions

Organisme : European Research Council
ID : ERC-2014-StG - 637830
Pays : International

Informations de copyright

© 2023. Springer Science+Business Media, LLC.

Références

N Engl J Med. 2013 May 23;368(21):1980-91
pubmed: 23697514
J Clin Med. 2020 Jun 16;9(6):
pubmed: 32560275
J Cancer. 2021 May 5;12(13):3862-3876
pubmed: 34093794
Biology (Basel). 2022 Jul 20;11(7):
pubmed: 36101460
Sci Rep. 2023 Apr 24;13(1):6620
pubmed: 37095155
Nat Commun. 2021 Feb 16;12(1):1072
pubmed: 33594057
Int J Clin Exp Pathol. 2020 Feb 01;13(2):163-171
pubmed: 32211096
J Breath Res. 2015 Dec 15;9(4):047112
pubmed: 26669903
Dev Cell. 2022 Aug 8;57(15):1866-1882.e10
pubmed: 35835117
Lancet. 1986 Feb 8;1(8476):307-10
pubmed: 2868172
Technol Cancer Res Treat. 2020 Jan-Dec;19:1533033820947490
pubmed: 32851926
Oncol Lett. 2018 Jul;16(1):247-252
pubmed: 29928408
Eur Respir J. 2017 Apr 26;49(4):
pubmed: 28446552
J Thorac Dis. 2020 May;12(5):2536-2544
pubmed: 32642161
J Thorac Oncol. 2016 Mar;11(3):300-11
pubmed: 26723244
J Gen Intern Med. 2020 Oct;35(10):3015-3025
pubmed: 32583338
J Thorac Oncol. 2019 Oct;14(10):1732-1742
pubmed: 31260833
BMC Biol. 2014 Mar 24;12:21
pubmed: 24661562
Bioinformatics. 2005 Oct 15;21(20):3940-1
pubmed: 16096348
N Engl J Med. 2006 Oct 26;355(17):1763-71
pubmed: 17065637
Environ Pollut. 2023 Jun 1;326:121463
pubmed: 36958658
Am J Respir Crit Care Med. 2015 May 15;191(10):1166-75
pubmed: 25760561
Front Genet. 2023 Jun 22;14:1200262
pubmed: 37424727
Lung. 2015 Dec;193(6):957-63
pubmed: 26260979
Theranostics. 2023 Apr 17;13(8):2384-2407
pubmed: 37215577
CA Cancer J Clin. 2018 Nov;68(6):394-424
pubmed: 30207593
Trends Mol Med. 2019 Apr;25(4):287-302
pubmed: 30795971
EMBO Mol Med. 2016 Dec 1;8(12):1380-1389
pubmed: 27821429
Oncogene. 2020 Apr;39(18):3726-3737
pubmed: 32157212
Prenat Diagn. 2023 Jan;43(1):28-35
pubmed: 36464942
Eur Respir J. 2005 Sep;26(3):523-48
pubmed: 16135737
Int J Clin Oncol. 2022 Apr;27(4):665-675
pubmed: 35020103

Auteurs

Karla Rubio (K)

Université de Lorraine, CNRS, Laboratoire IMoPA, UMR 7365, 54000, Nancy, France.
Lung Cancer Epigenetic, Max-Planck-Institute for Heart and Lung Research, 61231, Bad Nauheim, Germany.
Universities of Giessen and Marburg Lung Center (UGMLC), Giessen, Germany.
German Center for Lung Research (Deutsches Zentrum für Lungenforschung, DZL), Gießen, Germany.
Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, 02129, USA.
International Laboratory EPIGEN, Consejo de Ciencia y Tecnología del Estado de Puebla (CONCYTEP), Instituto de Ciencias, EcoCampus, Benemérita Universidad Autónoma de Puebla, 72570, Puebla, Mexico.

Jason M Müller (JM)

Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
Institute of Medical Statistics and Computational Biology, Faculty of Medicine, University of Cologne, Cologne, Germany.

Aditi Mehta (A)

German Center for Lung Research (Deutsches Zentrum für Lungenforschung, DZL), Gießen, Germany.
Pharmaceutical Technology and Biopharmaceutics, Department of Pharmacy, Ludwig-Maximilians-University (LMU) Munich, 81377, Munich, Germany.
Comprehensive Pneumology Center Munich (CPC-M), Munich, Germany.

Iris Watermann (I)

German Center for Lung Research (Deutsches Zentrum für Lungenforschung, DZL), Gießen, Germany.
LungenClinic Grosshansdorf (GHD), Airway Research Center North (ARCN), German Center for Lung Research (DZL), 22927, Großhansdorf, Germany.

Till Olchers (T)

German Center for Lung Research (Deutsches Zentrum für Lungenforschung, DZL), Gießen, Germany.
LungenClinic Grosshansdorf (GHD), Airway Research Center North (ARCN), German Center for Lung Research (DZL), 22927, Großhansdorf, Germany.

Ina Koch (I)

German Center for Lung Research (Deutsches Zentrum für Lungenforschung, DZL), Gießen, Germany.
Comprehensive Pneumology Center Munich (CPC-M), Munich, Germany.
Asklepios Biobank für Lungenerkrankungen, Asklepios Klinik Gauting GmbH, 82131, Gauting, Germany.

Sabine Wessels (S)

German Center for Lung Research (Deutsches Zentrum für Lungenforschung, DZL), Gießen, Germany.
Translational Research Unit, Thoraxklinik at Heidelberg University Hospital, 69126, Heidelberg, Germany.
Translational Lung Research Center Heidelberg (TLRC), 69120, Heidelberg, Germany.

Marc A Schneider (MA)

German Center for Lung Research (Deutsches Zentrum für Lungenforschung, DZL), Gießen, Germany.
Translational Research Unit, Thoraxklinik at Heidelberg University Hospital, 69126, Heidelberg, Germany.
Translational Lung Research Center Heidelberg (TLRC), 69120, Heidelberg, Germany.

Tania Araujo-Ramos (T)

German Cancer Research Center (DKFZ) Heidelberg, Division Chronic Inflammation and Cancer, Emmy Noether Research Group Epigenetic Machineries and Cancer, 69120, Heidelberg, Germany.

Indrabahadur Singh (I)

German Cancer Research Center (DKFZ) Heidelberg, Division Chronic Inflammation and Cancer, Emmy Noether Research Group Epigenetic Machineries and Cancer, 69120, Heidelberg, Germany.

Christian Kugler (C)

German Center for Lung Research (Deutsches Zentrum für Lungenforschung, DZL), Gießen, Germany.
LungenClinic Grosshansdorf (GHD), Airway Research Center North (ARCN), German Center for Lung Research (DZL), 22927, Großhansdorf, Germany.

Mircea Gabriel Stoleriu (MG)

German Center for Lung Research (Deutsches Zentrum für Lungenforschung, DZL), Gießen, Germany.
Comprehensive Pneumology Center Munich (CPC-M), Munich, Germany.
Asklepios Biobank für Lungenerkrankungen, Asklepios Klinik Gauting GmbH, 82131, Gauting, Germany.

Mark Kriegsmann (M)

German Center for Lung Research (Deutsches Zentrum für Lungenforschung, DZL), Gießen, Germany.
Translational Lung Research Center Heidelberg (TLRC), 69120, Heidelberg, Germany.
Institute of Pathology, University of Heidelberg, 69120, Heidelberg, Germany.

Martin Eichhorn (M)

German Center for Lung Research (Deutsches Zentrum für Lungenforschung, DZL), Gießen, Germany.
Translational Lung Research Center Heidelberg (TLRC), 69120, Heidelberg, Germany.
Department of Thoracic Surgery, University of Heidelberg, 69120, Heidelberg, Germany.

Thomas Muley (T)

German Center for Lung Research (Deutsches Zentrum für Lungenforschung, DZL), Gießen, Germany.
Translational Research Unit, Thoraxklinik at Heidelberg University Hospital, 69126, Heidelberg, Germany.
Translational Lung Research Center Heidelberg (TLRC), 69120, Heidelberg, Germany.

Olivia M Merkel (OM)

German Center for Lung Research (Deutsches Zentrum für Lungenforschung, DZL), Gießen, Germany.
Pharmaceutical Technology and Biopharmaceutics, Department of Pharmacy, Ludwig-Maximilians-University (LMU) Munich, 81377, Munich, Germany.
Comprehensive Pneumology Center Munich (CPC-M), Munich, Germany.

Thomas Braun (T)

Universities of Giessen and Marburg Lung Center (UGMLC), Giessen, Germany.
Department of Cardiac Development, Max-Planck-Institute for Heart and Lung Research, 61231, Bad Nauheim, Germany.

Ole Ammerpohl (O)

German Center for Lung Research (Deutsches Zentrum für Lungenforschung, DZL), Gießen, Germany.
Institute of Human Genetics, University Medical Center Ulm, 89081, Ulm, Germany.

Martin Reck (M)

German Center for Lung Research (Deutsches Zentrum für Lungenforschung, DZL), Gießen, Germany.
LungenClinic Grosshansdorf (GHD), Airway Research Center North (ARCN), German Center for Lung Research (DZL), 22927, Großhansdorf, Germany.

Achim Tresch (A)

Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany. achim.tresch@uni-koeln.de.
Institute of Medical Statistics and Computational Biology, Faculty of Medicine, University of Cologne, Cologne, Germany. achim.tresch@uni-koeln.de.
Center for Data and Simulation Science, University of Cologne, Cologne, Germany. achim.tresch@uni-koeln.de.

Guillermo Barreto (G)

Université de Lorraine, CNRS, Laboratoire IMoPA, UMR 7365, 54000, Nancy, France. guillermo.barreto@univ-lorraine.fr.
Lung Cancer Epigenetic, Max-Planck-Institute for Heart and Lung Research, 61231, Bad Nauheim, Germany. guillermo.barreto@univ-lorraine.fr.
Universities of Giessen and Marburg Lung Center (UGMLC), Giessen, Germany. guillermo.barreto@univ-lorraine.fr.
German Center for Lung Research (Deutsches Zentrum für Lungenforschung, DZL), Gießen, Germany. guillermo.barreto@univ-lorraine.fr.

Classifications MeSH