Skip to main content

Main menu

  • Home
  • Current issue
  • ERJ Early View
  • Past issues
  • ERS Guidelines
  • Authors/reviewers
    • Instructions for authors
    • Submit a manuscript
    • Open access
    • Peer reviewer login
  • Alerts
  • Subscriptions
  • ERS Publications
    • European Respiratory Journal
    • ERJ Open Research
    • European Respiratory Review
    • Breathe
    • ERS Books
    • ERS publications home

User menu

  • Log in
  • Subscribe
  • Contact Us
  • My Cart

Search

  • Advanced search
  • ERS Publications
    • European Respiratory Journal
    • ERJ Open Research
    • European Respiratory Review
    • Breathe
    • ERS Books
    • ERS publications home

Login

European Respiratory Society

Advanced Search

  • Home
  • Current issue
  • ERJ Early View
  • Past issues
  • ERS Guidelines
  • Authors/reviewers
    • Instructions for authors
    • Submit a manuscript
    • Open access
    • Peer reviewer login
  • Alerts
  • Subscriptions

Prognostic phenotypes of early-stage lung adenocarcinoma

Anne-Sophie Lamort, Jan Christian Kaiser, Mario A.A. Pepe, Ioannis Lilis, Giannoula Ntaliarda, Kalman Somogyi, Magda Spella, Sabine J. Behrend, Georgia A. Giotopoulou, Willem Kujawa, Michael Lindner, Ina Koch, Rudolf A. Hatz, Juergen Behr, Rocio Sotillo, Andrea C. Schamberger, Georgios T. Stathopoulos
European Respiratory Journal 2022 60: 2101674; DOI: 10.1183/13993003.01674-2021
Anne-Sophie Lamort
1Comprehensive Pneumology Center (CPC) and Institute for Lung Biology and Disease (iLBD), Helmholtz Center Munich–German Research Center for Environmental Health (HMGU), Munich, Germany
2German Center for Lung Research, Giessen, Germany
9These authors contributed equally to this work
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jan Christian Kaiser
3Institute of Radiation Medicine (IRM), Helmholtz Center Munich–German Research Center for Environmental Health (HMGU), Neuherberg, Germany
9These authors contributed equally to this work
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Jan Christian Kaiser
Mario A.A. Pepe
1Comprehensive Pneumology Center (CPC) and Institute for Lung Biology and Disease (iLBD), Helmholtz Center Munich–German Research Center for Environmental Health (HMGU), Munich, Germany
2German Center for Lung Research, Giessen, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ioannis Lilis
4Dept of Physiology, Faculty of Medicine, University of Patras, Rio, Greece
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Ioannis Lilis
Giannoula Ntaliarda
4Dept of Physiology, Faculty of Medicine, University of Patras, Rio, Greece
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Giannoula Ntaliarda
Kalman Somogyi
2German Center for Lung Research, Giessen, Germany
5Division of Molecular Thoracic Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Magda Spella
4Dept of Physiology, Faculty of Medicine, University of Patras, Rio, Greece
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sabine J. Behrend
1Comprehensive Pneumology Center (CPC) and Institute for Lung Biology and Disease (iLBD), Helmholtz Center Munich–German Research Center for Environmental Health (HMGU), Munich, Germany
2German Center for Lung Research, Giessen, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Sabine J. Behrend
Georgia A. Giotopoulou
1Comprehensive Pneumology Center (CPC) and Institute for Lung Biology and Disease (iLBD), Helmholtz Center Munich–German Research Center for Environmental Health (HMGU), Munich, Germany
2German Center for Lung Research, Giessen, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Willem Kujawa
1Comprehensive Pneumology Center (CPC) and Institute for Lung Biology and Disease (iLBD), Helmholtz Center Munich–German Research Center for Environmental Health (HMGU), Munich, Germany
2German Center for Lung Research, Giessen, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michael Lindner
2German Center for Lung Research, Giessen, Germany
6Center for Thoracic Surgery Munich, Ludwig Maximilian University of Munich and Asklepios Medical Center, Gauting, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ina Koch
2German Center for Lung Research, Giessen, Germany
6Center for Thoracic Surgery Munich, Ludwig Maximilian University of Munich and Asklepios Medical Center, Gauting, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rudolf A. Hatz
2German Center for Lung Research, Giessen, Germany
6Center for Thoracic Surgery Munich, Ludwig Maximilian University of Munich and Asklepios Medical Center, Gauting, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Juergen Behr
2German Center for Lung Research, Giessen, Germany
7Dept of Medicine V, University Hospital, Ludwig Maximilian University of Munich, Munich, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rocio Sotillo
2German Center for Lung Research, Giessen, Germany
5Division of Molecular Thoracic Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany
8Translational Lung Research Center Heidelberg (TRLC), German Center for Lung Research (DZL), Heidelberg, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Andrea C. Schamberger
1Comprehensive Pneumology Center (CPC) and Institute for Lung Biology and Disease (iLBD), Helmholtz Center Munich–German Research Center for Environmental Health (HMGU), Munich, Germany
2German Center for Lung Research, Giessen, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Georgios T. Stathopoulos
1Comprehensive Pneumology Center (CPC) and Institute for Lung Biology and Disease (iLBD), Helmholtz Center Munich–German Research Center for Environmental Health (HMGU), Munich, Germany
2German Center for Lung Research, Giessen, Germany
9These authors contributed equally to this work
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Georgios T. Stathopoulos
  • For correspondence: stathopoulos@helmholtz-muenchen.de
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

Abstract

Background Survival after curative resection of early-stage lung adenocarcinoma (LUAD) varies and prognostic biomarkers are urgently needed.

Methods Large-format tissue samples from a prospective cohort of 200 patients with resected LUAD were immunophenotyped for cancer hallmarks TP53, NF1, CD45, PD-1, PCNA, TUNEL and FVIII, and were followed for a median of 2.34 (95% CI 1.71–3.49) years.

Results Unsupervised hierarchical clustering revealed two patient subgroups with similar clinicopathological features and genotype, but with markedly different survival: “proliferative” patients (60%) with elevated TP53, NF1, CD45 and PCNA expression had 50% 5-year overall survival, while “apoptotic” patients (40%) with high TUNEL had 70% 5-year survival (hazard ratio 2.23, 95% CI 1.33–3.80; p=0.0069). Cox regression and machine learning algorithms including random forests built clinically useful models: a score to predict overall survival and a formula and nomogram to predict tumour phenotype. The distinct LUAD phenotypes were validated in The Cancer Genome Atlas and KMplotter data, and showed prognostic power supplementary to International Association for the Study of Lung Cancer tumour–node–metastasis stage and World Health Organization histologic classification.

Conclusions Two molecular subtypes of LUAD exist and their identification provides important prognostic information.

Abstract

Clinical-grade immunodetection of TP53, NF1, CD45, PD-1, PCNA, TUNEL and FVIII in tumour samples identifies two phenotypes of resected lung adenocarcinomas that display different prognosis and can be used for patient management and trial design https://bit.ly/3DpM5Ll

Footnotes

  • Author contributions: M. Lindner, I. Koch and R.A. Hatz performed surgeries and procured data that were produced during surgeries. J. Behr performed clinical and physiological assessment. M.A.A. Pepe, M. Spella, I. Lilis, G. Ntaliarda, S.J. Behrend, G.A. Giotopoulou and A.C. Schamberger processed samples and provided important intellectual input. A-S. Lamort and W. Kujawa performed IHC. M.A.A. Pepe performed digital droplet PCR and analysed data; K. Somogyi and R. Sotillo analysed ALK fusions. A-S. Lamort, J.C. Kaiser and G.T. Stathopoulos designed and guided the study, analysed data, and wrote the manuscript. All authors critically reviewed and edited the paper for important intellectual content and approved the final submitted version. A-S. Lamort, J.C. Kaiser and G.T. Stathopoulos had full access to all the data of the study, had final responsibility for the decision to submit it for publication and are the guarantors of the study's integrity.

  • This article has an editorial commentary: https://doi.org/10.1183/13993003.00569-2022

  • This study is registered at the German Clinical Trials Register with identifier number DRKS00012649.

  • Conflict of interest: The authors declare no potential conflicts of interest.

  • Support statement: This work was supported by European Research Council 2010 Starting Independent Investigator (260524) and 2015 Proof of Concept (679345) grants, the Graduate College (Graduiertenkolleg) 2338 of the German Research Society (Deutsche Forschungsgemeinschaft), the target validation project for pharmaceutical development ALTERNATIVE of the German Ministry for Education and Research (Bundesministerium für Bildung und Forschung), and a Translational Research Grant by the German Center for Lung Research (Deutsches Zentrum für Lungenforschung) (all to G.T. Stathopoulos). The study sponsors had no role in study design, data collection, analysis and interpretation, and in writing and submitting the paper for publication. Funding information for this article has been deposited with the Crossref Funder Registry.

  • Received June 14, 2021.
  • Accepted November 11, 2021.
  • Copyright ©The authors 2022. For reproduction rights and permissions contact permissions{at}ersnet.org
https://www.ersjournals.com/user-licence
View Full Text

ERS Members

myERS - ERS members : log in with your myERS username and password.

INDIVIDUALS

Log in Login as an individual user.

Forgot your username or password?

LIBRARY USERS

Log in through your institution

If your library has a subscription, you may already be logged in via your IP address. Otherwise you may be able to log in via one of the following routes.
You may be able to gain access using your login credentials for your institution. Contact your library if you do not have a username and password.
If your organization uses OpenAthens, you can log in using your OpenAthens username and password. To check if your institution is supported, please see this list. Contact your library for more details.
If you think you should have access, please contact your librarian or email journals@ersnet.org

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top
View this article with LENS
Vol 60 Issue 1 Table of Contents
European Respiratory Journal: 60 (1)
  • Table of Contents
  • Index by author
Email

Thank you for your interest in spreading the word on European Respiratory Society .

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Prognostic phenotypes of early-stage lung adenocarcinoma
(Your Name) has sent you a message from European Respiratory Society
(Your Name) thought you would like to see the European Respiratory Society web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Print
Citation Tools
Prognostic phenotypes of early-stage lung adenocarcinoma
Anne-Sophie Lamort, Jan Christian Kaiser, Mario A.A. Pepe, Ioannis Lilis, Giannoula Ntaliarda, Kalman Somogyi, Magda Spella, Sabine J. Behrend, Georgia A. Giotopoulou, Willem Kujawa, Michael Lindner, Ina Koch, Rudolf A. Hatz, Juergen Behr, Rocio Sotillo, Andrea C. Schamberger, Georgios T. Stathopoulos
European Respiratory Journal Jul 2022, 60 (1) 2101674; DOI: 10.1183/13993003.01674-2021

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
Prognostic phenotypes of early-stage lung adenocarcinoma
Anne-Sophie Lamort, Jan Christian Kaiser, Mario A.A. Pepe, Ioannis Lilis, Giannoula Ntaliarda, Kalman Somogyi, Magda Spella, Sabine J. Behrend, Georgia A. Giotopoulou, Willem Kujawa, Michael Lindner, Ina Koch, Rudolf A. Hatz, Juergen Behr, Rocio Sotillo, Andrea C. Schamberger, Georgios T. Stathopoulos
European Respiratory Journal Jul 2022, 60 (1) 2101674; DOI: 10.1183/13993003.01674-2021
del.icio.us logo Digg logo Reddit logo Technorati logo Twitter logo CiteULike logo Connotea logo Facebook logo Google logo Mendeley logo
Full Text (PDF)

Jump To

  • Article
    • Abstract
    • Abstract
    • Introduction
    • Materials and methods
    • Results
    • Discussion
    • Supplementary material
    • Shareable PDF
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • PDF

Subjects

  • Lung cancer
  • Tweet Widget
  • Facebook Like
  • Google Plus One

More in this TOC Section

Original Research Articles

  • Effects of sotatercept on haemodynamics and right heart function
  • Severe asddddddddddddddddddddddarasthma trajectories in adults: NORDSTAR cohort
  • High-dose versus low-dose prednisolone for treating sarcoidosis
Show more Original Research Articles

Lung cancer

  • Prognostic factors in non-small cell lung cancer
  • Hyperoxia suppresses lung cancer metastasis through MYC/SLC1A5 pathway
  • Participation in community-based lung cancer screening
Show more Lung cancer

Related Articles

Navigate

  • Home
  • Current issue
  • Archive

About the ERJ

  • Journal information
  • Editorial board
  • Press
  • Permissions and reprints
  • Advertising

The European Respiratory Society

  • Society home
  • myERS
  • Privacy policy
  • Accessibility

ERS publications

  • European Respiratory Journal
  • ERJ Open Research
  • European Respiratory Review
  • Breathe
  • ERS books online
  • ERS Bookshop

Help

  • Feedback

For authors

  • Instructions for authors
  • Publication ethics and malpractice
  • Submit a manuscript

For readers

  • Alerts
  • Subjects
  • Podcasts
  • RSS

Subscriptions

  • Accessing the ERS publications

Contact us

European Respiratory Society
442 Glossop Road
Sheffield S10 2PX
United Kingdom
Tel: +44 114 2672860
Email: journals@ersnet.org

ISSN

Print ISSN:  0903-1936
Online ISSN: 1399-3003

Copyright © 2023 by the European Respiratory Society