Non-invasive lung cancer diagnosis by detection of GATA6 and NKX2-1 isoforms in exhaled breath condensate.
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.
LOEWE Research Group Lung Cancer Epigenetic, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
Aditi
A
Mehta
LOEWE Research Group Lung Cancer Epigenetic, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
Julio
J
Cordero
LOEWE Research Group Lung Cancer Epigenetic, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
Stephanie
S
Dobersch
LOEWE Research Group Lung Cancer Epigenetic, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.|Facultad de Ciencias Químicas, Universidad Autonoma "Benito Juarez" de Oaxaca, Oaxaca, Mexico.
Addi J
AJ
Romero-Olmedo
Department of Lung Development and Remodeling, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.|Pulmonary and Critical Care Medicine, Department of Internal Medicine, Justus Liebig University, Giessen, Germany.
Rajkumar
R
Savai
Section Thoracic Surgery, Justus Liebig University, Giessen, Germany.
Johannes
J
Bodner
Chair for Lung Matrix Remodeling, Excellence Cluster Cardio Pulmonary System, Justus Liebig University, Giessen, Germany.
Cho-Ming
CM
Chao
Institute of Pathology and Cytology, UEGP, Wetzlar, Germany.
Ludger
L
Fink
Regional Hospital of High Specialties of Oaxaca (HRAEO), Oaxaca, Mexico.
Ernesto
E
Guzmán-Díaz
LOEWE Research Group Lung Cancer Epigenetic, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
Indrabahadur
I
Singh
Emmy Noether Research Group Origin of Cardiac Cell Lineages, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
Gergana
G
Dobreva
Department of Lung Development and Remodeling, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
Ulf R
UR
Rapp
Department of Cardiac Development and Remodeling, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
Stefan
S
Günther
Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, Kazan, Russian Federation.
Olga N
ON
Ilinskaya
Chair for Lung Matrix Remodeling, Excellence Cluster Cardio Pulmonary System, Justus Liebig University, Giessen, Germany.|Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, Kazan, Russian Federation.
Saverio
S
Bellusci
Institute for Genetics, Justus Liebig University, Giessen, Germany.
Reinhard H
RH
Dammann
Department of Cardiac Development and Remodeling, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
Thomas
T
Braun
Department of Lung Development and Remodeling, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.|Pulmonary and Critical Care Medicine, Department of Internal Medicine, Justus Liebig University, Giessen, Germany.
Werner
W
Seeger
Institute for Pathology, Justus Liebig University, Giessen, Germany.
Stefan
S
Gattenlöhner
Max Planck Institute for Plant Breeding Research, Cologne, Germany.|University of Cologne, Cologne, Germany.
Achim
A
Tresch
Pulmonary and Critical Care Medicine, Department of Internal Medicine, Justus Liebig University, Giessen, Germany.|Agaplesion Lung Clinic Waldhof Elgershausen, Greifenstein, Germany.
Andreas
A
Günther
LOEWE Research Group Lung Cancer Epigenetic, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany guillermo.barreto@mpi-bn.mpg.de.|Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, Kazan, Russian Federation.
Guillermo
0000-0002-7777-4712
G
Barreto
D001944:Breath Tests / Q000379:methods*; D016022:Case-Control Studies; D003661:Decision Support Techniques; D050993:GATA6 Transcription Factor / Q000032:analysis*; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000473:pathology; D009687:Nuclear Proteins / Q000032:analysis*; D011446:Prospective Studies; D020033:Protein Isoforms / Q000032:analysis; D012189:Retrospective Studies; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000032:analysis*
D050993:GATA6 Transcription Factor; C494759:GATA6 protein, human; D009687:Nuclear Proteins; D020033:Protein Isoforms; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors

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