Non-invasive lung cancer diagnosis by detection of GATA6 and NKX2-1 isoforms in exhaled breath condensate

  • EMBO Mol Med. 2016 Dec 1;8(12):1380-1389. doi: 10.15252/emmm.201606382.
Aditi Mehta  1 ,  Julio Cordero  1 ,  Stephanie Dobersch  1 ,  Addi J Romero-Olmedo  1  2 ,  Rajkumar Savai  3  4 ,  Johannes Bodner  5 ,  Cho-Ming Chao  6 ,  Ludger Fink  7 ,  Ernesto Guzmán-Díaz  8 ,  Indrabahadur Singh  1 ,  Gergana Dobreva  9 ,  Ulf R Rapp  3 ,  Stefan Günther  10 ,  Olga N Ilinskaya  11 ,  Saverio Bellusci  6  11 ,  Reinhard H Dammann  12 ,  Thomas Braun  10 ,  Werner Seeger  3  4 ,  Stefan Gattenlöhner  13 ,  Achim Tresch  14  15 ,  Andreas Günther  4  16 ,  Guillermo Barreto  17  11
Affiliations
  • 1. LOEWE Research Group Lung Cancer Epigenetic, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
  • 2. Facultad de Ciencias Químicas, Universidad Autonoma "Benito Juarez" de Oaxaca, Oaxaca, Mexico.
  • 3. Department of Lung Development and Remodeling, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
  • 4. Pulmonary and Critical Care Medicine, Department of Internal Medicine, Justus Liebig University, Giessen, Germany.
  • 5. Section Thoracic Surgery, Justus Liebig University, Giessen, Germany.
  • 6. Chair for Lung Matrix Remodeling, Excellence Cluster Cardio Pulmonary System, Justus Liebig University, Giessen, Germany.
  • 7. Institute of Pathology and Cytology, UEGP, Wetzlar, Germany.
  • 8. Regional Hospital of High Specialties of Oaxaca (HRAEO), Oaxaca, Mexico.
  • 9. Emmy Noether Research Group Origin of Cardiac Cell Lineages, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
  • 10. Department of Cardiac Development and Remodeling, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
  • 11. Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, Kazan, Russian Federation.
  • 12. Institute for Genetics, Justus Liebig University, Giessen, Germany.
  • 13. Institute for Pathology, Justus Liebig University, Giessen, Germany.
  • 14. Max Planck Institute for Plant Breeding Research, Cologne, Germany.
  • 15. University of Cologne, Cologne, Germany.
  • 16. Agaplesion Lung Clinic Waldhof Elgershausen, Greifenstein, Germany.
  • 17. LOEWE Research Group Lung Cancer Epigenetic, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany [email protected].
PMID: 27821429 DOI: 10.15252/emmm.201606382
Abstract

Lung Cancer (LC) is the leading cause of cancer-related deaths worldwide. Early LC diagnosis is crucial to reduce the high case fatality rate of this disease. In this case-control study, we developed an accurate LC diagnosis test using retrospectively collected formalin-fixed paraffin-embedded (FFPE) human lung tissues and prospectively collected exhaled breath condensates (EBCs). Following international guidelines for diagnostic methods with clinical application, reproducible standard operating procedures (SOP) were established for every step comprising our LC diagnosis method. We analyzed the expression of distinct mRNAs expressed from GATA6 and NKX2-1, key regulators of lung development. The Em/Ad expression ratios of GATA6 and NKX2-1 detected in EBCs were combined using linear kernel support vector machines (SVM) into the LC score, which can be used for LC detection. LC score-based diagnosis achieved a high performance in an independent validation cohort. We propose our method as a non-invasive, accurate, and low-price option to complement the success of computed tomography imaging (CT) and chest X-ray (CXR) for LC diagnosis.

Keywords
EBC; GATA6; NKX2‐1; lung cancer; molecular diagnostics.