Evidence map›Paper›PMID 37592303›Full record

ArticleJournal of translational medicine2023

The tight junction protein claudin 6 is a potential target for patient-individualized treatment in esophageal and gastric adenocarcinoma and is associated with poor prognosis.

Adrian Georg Simon, Su Ir Lyu, Mark Laible, Stefan Wöll, Özlem Türeci, Uğur Şahin, Hakan Alakus, Luca Fahrig, Thomas Zander, Reinhard Buettner and 4 more

2 registry-linked trialsOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of translational medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
2.9field-weighted citation impact, top 8% of its field
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.

NCT04503278 phase1active not recruitingnot on this map

Phase I/IIa, First-in-human, Open-label, Dose Escalation Trial With Expansion Cohorts to Evaluate Safety and Preliminary Efficacy of CLDN6 CAR-T With or Without CLDN6 RNA-LPX in Patients With CLDN6-positive Relapsed or Refractory Advanced Solid Tumors

TypeinterventionalSponsorBioNTech Cell & Gene Therapies GmbHRan2020 to 2041Enrolled214ConditionsSolid TumorArmsCLDN6 CAR-T, CLDN6 uRNA-LPX/CLDN6 modRNA-LPX
NCT05262530 phase1 / phase2terminatednot on this map

First-in-human, Open-label, Multicenter, Phase I/IIa, Dose Escalation Trial With Expansion Cohorts to Evaluate Safety and Preliminary Efficacy of BNT142 in Patients With CLDN6-positive Advanced Solid Tumors

TypeinterventionalSponsorBioNTech SERan2022 to 2025Enrolled73ConditionsSolid TumorArmsBNT142
3 · Its place in the literature

Who cites it

18 citing papers in PubMed, 24 citations in OpenAlex.

  1. Article
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  8. ComprehensiveOncology reports · 2025
    Review
  9. Article
  10. Review
  11. Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2025
    Article
  12. Review
  13. Review
  14. Review
  15. Article
  16. HER2International journal of oncology · 2024
    Review
  17. mJournal of hepatocellular carcinoma · 2024
    Article
  18. Review
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

14 authors at 2 institutions in 1 country.

Adrian Georg SimonInstitute of Pathology, University Hospital Cologne, Medical Faculty, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany. adrian.simon@uk-koeln.de.ORCID http://orcid.org/0000-0002-2709-863X
Su Ir LyuInstitute of Pathology, University Hospital Cologne, Medical Faculty, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany.
Mark LaibleBioNTech SE, Mainz, Germany.
Stefan WöllBioNTech SE, Mainz, Germany.
Özlem TüreciBioNTech SE, Mainz, Germany.
Uğur ŞahinBioNTech SE, Mainz, Germany.
Hakan AlakusDepartment of General, Visceral and Cancer Surgery, University Hospital Cologne, Medical Faculty, University of Cologne, Cologne, Germany.
Luca FahrigDepartment of General, Visceral and Cancer Surgery, University Hospital Cologne, Medical Faculty, University of Cologne, Cologne, Germany.
Thomas ZanderDepartment of Internal Medicine I, University Hospital Cologne, Medical Faculty, University of Cologne, Cologne, Germany.
Reinhard BuettnerInstitute of Pathology, University Hospital Cologne, Medical Faculty, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany.
Christiane Josephine BrunsDepartment of General, Visceral and Cancer Surgery, University Hospital Cologne, Medical Faculty, University of Cologne, Cologne, Germany.
Wolfgang SchroederDepartment of General, Visceral and Cancer Surgery, University Hospital Cologne, Medical Faculty, University of Cologne, Cologne, Germany.
Florian GebauerDepartment of General, Visceral and Cancer Surgery, University Hospital Cologne, Medical Faculty, University of Cologne, Cologne, Germany.
Alexander QuaasInstitute of Pathology, University Hospital Cologne, Medical Faculty, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany.
University of Cologne · DEBioNTech (Germany) · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe prognosis of esophageal adenocarcinoma (EAC) and gastric adenocarcinoma (GAC) remains poor, and new therapeutic approaches are urgently needed. Claudin 6 (CLDN6) is an oncofetal antigen that is largely absent in healthy tissues and upregulated in several cancers, making it a promising therapeutical target. In this study, the expression of CLDN6 was assessed in an large Caucasian EAC and GAC cohort.

methodsRNA-Seq data from 89 EACs and 371 GACs were obtained from The Cancer Genome Atlas project and EAC/GAC cases were stratified by CLDN6 mRNA expression based on a survival-associated cutoff. For groups with CLDN6 expression above or below this cutoff, differential gene expression analyses were performed using DESeq, and dysregulated biological pathways were identified using the Enrichr tool. Additionally, CLDN6 protein expression was assessed in more than 800 EACs and almost 600 GACs using a CLDN6-specific immunohistochemical antibody (clone 58-4B-2) that is currently used in Phase I/II trials to identify patients with CLDN6-positive tumors (NCT05262530; NCT04503278). The expression of CLDN6 was also correlated with histopathological parameters and overall survival (OS).

resultsEACs and GACs with high CLDN6 mRNA levels displayed an overexpression of pathways regulating the cell cycle, DNA replication, and receptor / extracellular matrix interactions. CLDN6 protein expression was associated with shorter OS in EAC and GAC, both in treatment-naïve subgroups and cohorts receiving neoadjuvant therapy. In multivariate analysis, CLDN6 protein expression was an independent adverse prognostic factor in EAC associated with a shorter OS (HR: 1.75; p = 0.01) and GAC (HR: 2.74; p = 0.028).

conclusionsHigh expression of CLDN6 mRNA is associated with the dysregulation of distinct biological pathways regulating cell growth, proliferation, and cell-matrix interactions. Clinically, the expression of CLDN6 protein is a valuable adverse prognostic marker in EAC and GAC.

Indexed as

AdenocarcinomaStomach NeoplasmsAminocaproic AcidAntibodiesClaudinsEsophageal NeoplasmsHumansTight Junction ProteinsAminocaproic AcidAntibodiesclaudin 6ClaudinsTight Junction ProteinsAdenocarcinomaCAR T-cell therapyClaudinCLDN6Esophageal cancerGastric cancerImmunotherapyTight junctions

Identifiers

PMID37592303
PMCPMC10436499
OpenAlexW4385964310

What OpenQuestion holds

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Registered trials

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 OpenQuestion graph.