Comparative proteomics reveals a diagnostic signature for pulmonary head‐and‐neck cancer metastasis

Abstract Patients with head‐and‐neck cancer can develop both lung metastasis and primary lung cancer during the course of their disease. Despite the clinical importance of discrimination, reliable diagnostic biomarkers are still lacking. Here, we have characterised a cohort of squamous cell lung (SQ...

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Main Authors: Hanibal Bohnenberger, Lars Kaderali, Philipp Ströbel, Diego Yepes, Uwe Plessmann, Neekesh V Dharia, Sha Yao, Carina Heydt, Sabine Merkelbach‐Bruse, Alexander Emmert, Jonatan Hoffmann, Julius Bodemeyer, Kirsten Reuter‐Jessen, Anna‐Maria Lois, Leif Hendrik Dröge, Philipp Baumeister, Christoph Walz, Lorenz Biggemann, Roland Walter, Björn Häupl, Federico Comoglio, Kuan‐Ting Pan, Sebastian Scheich, Christof Lenz, Stefan Küffer, Felix Bremmer, Julia Kitz, Maren Sitte, Tim Beißbarth, Marc Hinterthaner, Martin Sebastian, Joachim Lotz, Hans‐Ulrich Schildhaus, Hendrik Wolff, Bernhard C Danner, Christian Brandts, Reinhard Büttner, Martin Canis, Kimberly Stegmaier, Hubert Serve, Henning Urlaub, Thomas Oellerich
Format: Article
Language:English
Published: Springer Nature 2018-08-01
Series:EMBO Molecular Medicine
Subjects:
Online Access:https://doi.org/10.15252/emmm.201708428
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author Hanibal Bohnenberger
Lars Kaderali
Philipp Ströbel
Diego Yepes
Uwe Plessmann
Neekesh V Dharia
Sha Yao
Carina Heydt
Sabine Merkelbach‐Bruse
Alexander Emmert
Jonatan Hoffmann
Julius Bodemeyer
Kirsten Reuter‐Jessen
Anna‐Maria Lois
Leif Hendrik Dröge
Philipp Baumeister
Christoph Walz
Lorenz Biggemann
Roland Walter
Björn Häupl
Federico Comoglio
Kuan‐Ting Pan
Sebastian Scheich
Christof Lenz
Stefan Küffer
Felix Bremmer
Julia Kitz
Maren Sitte
Tim Beißbarth
Marc Hinterthaner
Martin Sebastian
Joachim Lotz
Hans‐Ulrich Schildhaus
Hendrik Wolff
Bernhard C Danner
Christian Brandts
Reinhard Büttner
Martin Canis
Kimberly Stegmaier
Hubert Serve
Henning Urlaub
Thomas Oellerich
author_facet Hanibal Bohnenberger
Lars Kaderali
Philipp Ströbel
Diego Yepes
Uwe Plessmann
Neekesh V Dharia
Sha Yao
Carina Heydt
Sabine Merkelbach‐Bruse
Alexander Emmert
Jonatan Hoffmann
Julius Bodemeyer
Kirsten Reuter‐Jessen
Anna‐Maria Lois
Leif Hendrik Dröge
Philipp Baumeister
Christoph Walz
Lorenz Biggemann
Roland Walter
Björn Häupl
Federico Comoglio
Kuan‐Ting Pan
Sebastian Scheich
Christof Lenz
Stefan Küffer
Felix Bremmer
Julia Kitz
Maren Sitte
Tim Beißbarth
Marc Hinterthaner
Martin Sebastian
Joachim Lotz
Hans‐Ulrich Schildhaus
Hendrik Wolff
Bernhard C Danner
Christian Brandts
Reinhard Büttner
Martin Canis
Kimberly Stegmaier
Hubert Serve
Henning Urlaub
Thomas Oellerich
author_sort Hanibal Bohnenberger
collection DOAJ
description Abstract Patients with head‐and‐neck cancer can develop both lung metastasis and primary lung cancer during the course of their disease. Despite the clinical importance of discrimination, reliable diagnostic biomarkers are still lacking. Here, we have characterised a cohort of squamous cell lung (SQCLC) and head‐and‐neck (HNSCC) carcinomas by quantitative proteomics. In a training cohort, we quantified 4,957 proteins in 44 SQCLC and 30 HNSCC tumours. A total of 518 proteins were found to be differentially expressed between SQCLC and HNSCC, and some of these were identified as genetic dependencies in either of the two tumour types. Using supervised machine learning, we inferred a proteomic signature for the classification of squamous cell carcinomas as either SQCLC or HNSCC, with diagnostic accuracies of 90.5% and 86.8% in cross‐ and independent validations, respectively. Furthermore, application of this signature to a cohort of pulmonary squamous cell carcinomas of unknown origin leads to a significant prognostic separation. This study not only provides a diagnostic proteomic signature for classification of secondary lung tumours in HNSCC patients, but also represents a proteomic resource for HNSCC and SQCLC.
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publishDate 2018-08-01
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series EMBO Molecular Medicine
spelling doaj-art-9e1b98ca39654a949c2bd368ebedd85e2025-08-20T04:03:02ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842018-08-0110911510.15252/emmm.201708428Comparative proteomics reveals a diagnostic signature for pulmonary head‐and‐neck cancer metastasisHanibal Bohnenberger0Lars Kaderali1Philipp Ströbel2Diego Yepes3Uwe Plessmann4Neekesh V Dharia5Sha Yao6Carina Heydt7Sabine Merkelbach‐Bruse8Alexander Emmert9Jonatan Hoffmann10Julius Bodemeyer11Kirsten Reuter‐Jessen12Anna‐Maria Lois13Leif Hendrik Dröge14Philipp Baumeister15Christoph Walz16Lorenz Biggemann17Roland Walter18Björn Häupl19Federico Comoglio20Kuan‐Ting Pan21Sebastian Scheich22Christof Lenz23Stefan Küffer24Felix Bremmer25Julia Kitz26Maren Sitte27Tim Beißbarth28Marc Hinterthaner29Martin Sebastian30Joachim Lotz31Hans‐Ulrich Schildhaus32Hendrik Wolff33Bernhard C Danner34Christian Brandts35Reinhard Büttner36Martin Canis37Kimberly Stegmaier38Hubert Serve39Henning Urlaub40Thomas Oellerich41Institute of Pathology, University Medical CenterInstitute of Bioinformatics, University Medicine GreifswaldInstitute of Pathology, University Medical CenterDepartment of Medicine II, Hematology/Oncology, Goethe UniversityBioanalytical Mass Spectrometry Group, Max Planck Institute for Biophysical ChemistryDepartment of Pediatric Oncology, Dana‐Farber Cancer InstituteInstitute of Pathology, University Medical CenterInstitute of Pathology, University Hospital Cologne, University of CologneInstitute of Pathology, University Hospital Cologne, University of CologneDepartment of Thoracic and Cardiovascular Surgery, University Medical CenterInstitute of Pathology, University Medical CenterInstitute of Pathology, University Medical CenterInstitute of Pathology, University Medical CenterInstitute of Pathology, University Medical CenterDepartment of Radiooncology, University Medical CenterDepartment of Otorhinolaryngology, University Hospital Munich, Ludwig‐Maximilian‐University MünchenInstitute of Pathology, Faculty of Medicine, LMU MunichInstitute for Diagnostic and Interventional Radiology, University Medical CenterDepartment of Medicine II, Hematology/Oncology, Goethe UniversityDepartment of Medicine II, Hematology/Oncology, Goethe UniversityDepartment of Haematology, University of CambridgeBioanalytical Mass Spectrometry Group, Max Planck Institute for Biophysical ChemistryDepartment of Medicine II, Hematology/Oncology, Goethe UniversityBioanalytical Mass Spectrometry Group, Max Planck Institute for Biophysical ChemistryInstitute of Pathology, University Medical CenterInstitute of Pathology, University Medical CenterInstitute of Pathology, University Medical CenterInstitute of Medical Statistics, University Medical CenterInstitute of Medical Statistics, University Medical CenterDepartment of Thoracic and Cardiovascular Surgery, University Medical CenterDepartment of Medicine II, Hematology/Oncology, Goethe UniversityInstitute for Diagnostic and Interventional Radiology, University Medical CenterInstitute of Pathology, University Medical CenterUniversity Medical CenterDepartment of Thoracic and Cardiovascular Surgery, University Medical CenterDepartment of Medicine II, Hematology/Oncology, Goethe UniversityInstitute of Pathology, University Hospital Cologne, University of CologneDepartment of Otorhinolaryngology, University Hospital Munich, Ludwig‐Maximilian‐University MünchenDepartment of Pediatric Oncology, Dana‐Farber Cancer InstituteDepartment of Medicine II, Hematology/Oncology, Goethe UniversityBioanalytical Mass Spectrometry Group, Max Planck Institute for Biophysical ChemistryDepartment of Medicine II, Hematology/Oncology, Goethe UniversityAbstract Patients with head‐and‐neck cancer can develop both lung metastasis and primary lung cancer during the course of their disease. Despite the clinical importance of discrimination, reliable diagnostic biomarkers are still lacking. Here, we have characterised a cohort of squamous cell lung (SQCLC) and head‐and‐neck (HNSCC) carcinomas by quantitative proteomics. In a training cohort, we quantified 4,957 proteins in 44 SQCLC and 30 HNSCC tumours. A total of 518 proteins were found to be differentially expressed between SQCLC and HNSCC, and some of these were identified as genetic dependencies in either of the two tumour types. Using supervised machine learning, we inferred a proteomic signature for the classification of squamous cell carcinomas as either SQCLC or HNSCC, with diagnostic accuracies of 90.5% and 86.8% in cross‐ and independent validations, respectively. Furthermore, application of this signature to a cohort of pulmonary squamous cell carcinomas of unknown origin leads to a significant prognostic separation. This study not only provides a diagnostic proteomic signature for classification of secondary lung tumours in HNSCC patients, but also represents a proteomic resource for HNSCC and SQCLC.https://doi.org/10.15252/emmm.201708428Biomarkerhead‐and‐neck cancerlung cancermetastasisproteomics
spellingShingle Hanibal Bohnenberger
Lars Kaderali
Philipp Ströbel
Diego Yepes
Uwe Plessmann
Neekesh V Dharia
Sha Yao
Carina Heydt
Sabine Merkelbach‐Bruse
Alexander Emmert
Jonatan Hoffmann
Julius Bodemeyer
Kirsten Reuter‐Jessen
Anna‐Maria Lois
Leif Hendrik Dröge
Philipp Baumeister
Christoph Walz
Lorenz Biggemann
Roland Walter
Björn Häupl
Federico Comoglio
Kuan‐Ting Pan
Sebastian Scheich
Christof Lenz
Stefan Küffer
Felix Bremmer
Julia Kitz
Maren Sitte
Tim Beißbarth
Marc Hinterthaner
Martin Sebastian
Joachim Lotz
Hans‐Ulrich Schildhaus
Hendrik Wolff
Bernhard C Danner
Christian Brandts
Reinhard Büttner
Martin Canis
Kimberly Stegmaier
Hubert Serve
Henning Urlaub
Thomas Oellerich
Comparative proteomics reveals a diagnostic signature for pulmonary head‐and‐neck cancer metastasis
EMBO Molecular Medicine
Biomarker
head‐and‐neck cancer
lung cancer
metastasis
proteomics
title Comparative proteomics reveals a diagnostic signature for pulmonary head‐and‐neck cancer metastasis
title_full Comparative proteomics reveals a diagnostic signature for pulmonary head‐and‐neck cancer metastasis
title_fullStr Comparative proteomics reveals a diagnostic signature for pulmonary head‐and‐neck cancer metastasis
title_full_unstemmed Comparative proteomics reveals a diagnostic signature for pulmonary head‐and‐neck cancer metastasis
title_short Comparative proteomics reveals a diagnostic signature for pulmonary head‐and‐neck cancer metastasis
title_sort comparative proteomics reveals a diagnostic signature for pulmonary head and neck cancer metastasis
topic Biomarker
head‐and‐neck cancer
lung cancer
metastasis
proteomics
url https://doi.org/10.15252/emmm.201708428
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