Evidence mapPaperPMID 38866964Full record

ArticleBritish journal of cancer2024

KRAS and TP53 co-mutation predicts benefit of immune checkpoint blockade in lung adenocarcinoma.

Jan Budczies, Eva Romanovsky, Martina Kirchner, Olaf Neumann, Miriam Blasi, Johannes Schnorbach, Rajiv Shah, Farastuk Bozorgmehr, Rajkumar Savai, Thorsten Stiewe and 6 more

Abstract read
In one paragraph

Article in British journal of cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

41 citing papers in PubMed.

  1. Article
  2. The AUTACE That Degrades KRAS and Engages CD8Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  3. Article
  4. Article
  5. Review
  6. Review
  7. Review
  8. Article
  9. Ultra-rare TP53 and KRAS variants predict survival in ICI-treated solid tumours.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Article
  10. Article
  11. Review
  12. Review
  13. Translational lung cancer research · 2026
    Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Jan BudcziesInstitute of Pathology, Heidelberg University Hospital, Heidelberg, Germany. jan.budczies@med.uni-heidelberg.de.ORCID http://orcid.org/0000-0002-6668-5327
Eva RomanovskyInstitute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.ORCID http://orcid.org/0000-0002-0059-1977
Martina KirchnerInstitute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.
Olaf NeumannInstitute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.ORCID http://orcid.org/0000-0003-2684-9187
Miriam BlasiTranslational Lung Research Center Heidelberg (TLRC-H), Member of the German Center for Lung Research (DZL), Heidelberg, Germany.
Johannes SchnorbachTranslational Lung Research Center Heidelberg (TLRC-H), Member of the German Center for Lung Research (DZL), Heidelberg, Germany.
Rajiv ShahTranslational Lung Research Center Heidelberg (TLRC-H), Member of the German Center for Lung Research (DZL), Heidelberg, Germany.
Farastuk BozorgmehrTranslational Lung Research Center Heidelberg (TLRC-H), Member of the German Center for Lung Research (DZL), Heidelberg, Germany.
Rajkumar SavaiInstitute for Lung Health (ILH), Justus Liebig University, Giessen, Germany.
Thorsten StieweInstitute of Molecular Oncology, Member of the German Center for Lung Research (DZL), Philipps-University, Marburg, Germany.ORCID http://orcid.org/0000-0003-0134-7826
Solange PetersDepartment of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne University, Lausanne, Switzerland.
Peter SchirmacherInstitute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.
Michael ThomasTranslational Lung Research Center Heidelberg (TLRC-H), Member of the German Center for Lung Research (DZL), Heidelberg, Germany.
Daniel KazdalInstitute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.ORCID http://orcid.org/0000-0001-8187-3281
Petros ChristopoulosTranslational Lung Research Center Heidelberg (TLRC-H), Member of the German Center for Lung Research (DZL), Heidelberg, Germany.ORCID http://orcid.org/0000-0002-7966-8980
Albrecht StenzingerInstitute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPredictive biomarkers in use for immunotherapy in advanced non-small cell lung cancer are of limited sensitivity and specificity. We analysed the potential of activating KRAS and pathogenic TP53 mutations to provide additional predictive information.

methodsThe study cohort included 713 consecutive immunotherapy patients with advanced lung adenocarcinomas, negative for actionable genetic alterations. Additionally, two previously published immunotherapy and two surgical patient cohorts were analyzed. Therapy benefit was stratified by KRAS and TP53 mutations. Molecular characteristics underlying KRASmut/TP53mut tumours were revealed by the analysis of TCGA data.

resultsAn interaction between KRAS and TP53 mutations was observed in univariate and multivariate analyses of overall survival (Hazard ratio [HR] = 0.56, p = 0.0044 and HR = 0.53, p = 0.0021) resulting in a stronger benefit for KRASmut/TP53mut tumours (HR = 0.71, CI 0.55-0.92). This observation was confirmed in immunotherapy cohorts but not observed in surgical cohorts. Tumour mutational burden, proliferation, and PD-L1 mRNA were significantly higher in TP53-mutated tumours, regardless of KRAS status. Genome-wide expression analysis revealed 64 genes, including CX3CL1 (fractalkine), as specific transcriptomic characteristic of KRASmut/TP53mut tumours.

conclusionsKRAS/TP53 co-mutation predicts ICI benefit in univariate and multivariate survival analyses and is associated with unique molecular tumour features. Mutation testing of the two genes can be easily implemented using small NGS panels.

Indexed as

Adenocarcinoma of LungImmune Checkpoint InhibitorsLung NeoplasmsMutationProto-Oncogene Proteins p21(ras)Tumor Suppressor Protein p53AdultAgedAged, 80 and overBiomarkers, TumorCohort StudiesFemaleHumansImmunotherapyMaleMiddle AgedBiomarkers, TumorImmune Checkpoint InhibitorsKRAS protein, humanProto-Oncogene Proteins p21(ras)TP53 protein, humanTumor Suppressor Protein p53

Identifiers

PMID38866964
PMCPMC11300455

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.