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

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

  • Discov Oncol. 2023 Oct 3;14(1):181. doi: 10.1007/s12672-023-00799-9.
Karla Rubio # 1 2 3 4 5 6 Jason M Müller # 7 8 Aditi Mehta 4 9 10 Iris Watermann 4 11 Till Olchers 4 11 Ina Koch 4 10 12 Sabine Wessels 4 13 14 Marc A Schneider 4 13 14 Tania Araujo-Ramos 15 Indrabahadur Singh 15 Christian Kugler 4 11 Mircea Gabriel Stoleriu 4 10 12 Mark Kriegsmann 4 14 16 Martin Eichhorn 4 14 17 Thomas Muley 4 13 14 Olivia M Merkel 4 9 10 Thomas Braun 3 18 Ole Ammerpohl 4 19 Martin Reck 4 11 Achim Tresch 20 21 22 Guillermo Barreto 23 24 25 26
Affiliations

Affiliations

  • 1 Université de Lorraine, CNRS, Laboratoire IMoPA, UMR 7365, 54000, Nancy, France.
  • 2 Lung Cancer Epigenetic, Max-Planck-Institute for Heart and Lung Research, 61231, Bad Nauheim, Germany.
  • 3 Universities of Giessen and Marburg Lung Center (UGMLC), Giessen, Germany.
  • 4 German Center for Lung Research (Deutsches Zentrum für Lungenforschung, DZL), Gießen, Germany.
  • 5 Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, 02129, USA.
  • 6 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.
  • 7 Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
  • 8 Institute of Medical Statistics and Computational Biology, Faculty of Medicine, University of Cologne, Cologne, Germany.
  • 9 Pharmaceutical Technology and Biopharmaceutics, Department of Pharmacy, Ludwig-Maximilians-University (LMU) Munich, 81377, Munich, Germany.
  • 10 Comprehensive Pneumology Center Munich (CPC-M), Munich, Germany.
  • 11 LungenClinic Grosshansdorf (GHD), Airway Research Center North (ARCN), German Center for Lung Research (DZL), 22927, Großhansdorf, Germany.
  • 12 Asklepios Biobank für Lungenerkrankungen, Asklepios Klinik Gauting GmbH, 82131, Gauting, Germany.
  • 13 Translational Research Unit, Thoraxklinik at Heidelberg University Hospital, 69126, Heidelberg, Germany.
  • 14 Translational Lung Research Center Heidelberg (TLRC), 69120, Heidelberg, Germany.
  • 15 German Cancer Research Center (DKFZ) Heidelberg, Division Chronic Inflammation and Cancer, Emmy Noether Research Group Epigenetic Machineries and Cancer, 69120, Heidelberg, Germany.
  • 16 Institute of Pathology, University of Heidelberg, 69120, Heidelberg, Germany.
  • 17 Department of Thoracic Surgery, University of Heidelberg, 69120, Heidelberg, Germany.
  • 18 Department of Cardiac Development, Max-Planck-Institute for Heart and Lung Research, 61231, Bad Nauheim, Germany.
  • 19 Institute of Human Genetics, University Medical Center Ulm, 89081, Ulm, Germany.
  • 20 Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany. achim.tresch@uni-koeln.de.
  • 21 Institute of Medical Statistics and Computational Biology, Faculty of Medicine, University of Cologne, Cologne, Germany. achim.tresch@uni-koeln.de.
  • 22 Center for Data and Simulation Science, University of Cologne, Cologne, Germany. achim.tresch@uni-koeln.de.
  • 23 Université de Lorraine, CNRS, Laboratoire IMoPA, UMR 7365, 54000, Nancy, France. guillermo.barreto@univ-lorraine.fr.
  • 24 Lung Cancer Epigenetic, Max-Planck-Institute for Heart and Lung Research, 61231, Bad Nauheim, Germany. guillermo.barreto@univ-lorraine.fr.
  • 25 Universities of Giessen and Marburg Lung Center (UGMLC), Giessen, Germany. guillermo.barreto@univ-lorraine.fr.
  • 26 German Center for Lung Research (Deutsches Zentrum für Lungenforschung, DZL), Gießen, Germany. guillermo.barreto@univ-lorraine.fr.
  • # Contributed equally.
Abstract

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: 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: 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: 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.

Keywords

Biomarker; Diagnostic; Exhaled breath condensate; GATA6; Lung cancer; NKX2-1.

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