Evidence map›Paper›PMID 31183506›Full record

ArticleJournal of molecular medicine (Berlin, Germany)2019

Heterogeneous intracellular TRAIL-receptor distribution predicts poor outcome in breast cancer patients.

Thorsten Heilmann, Florian Vondung, Christoph Borzikowsky, Silke Szymczak, Sandra Krüger, Ibrahim Alkatout, Antonia Wenners, Maret Bauer, Wolfram Klapper, Christoph Röcken and 4 more

Abstract read
PubMed Publisher
In one paragraph

Article in Journal of molecular medicine (Berlin, Germany), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.9field-weighted citation impact, top 26% 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.

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

9 citing papers in PubMed, 12 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Suppression of Ovarian Cancer Cell Growth by AT-MSC Microvesicles.International journal of molecular sciences · 2020
    Article
  8. Article
  9. 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 5 institutions in 1 country.

Thorsten HeilmannDepartment of Gynecology and Obstetrics, University Hospital Schleswig-Holstein, Kiel, Germany.
Florian VondungDepartment of Pathology, General Pathology and Hematopathology, University Hospital Schleswig-Holstein, Kiel, Germany.
Christoph BorzikowskyInstitute of Medical Informatics and Statistics, Christian-Albrechts-University of Kiel, Kiel, Germany.
Silke SzymczakInstitute of Medical Informatics and Statistics, Christian-Albrechts-University of Kiel, Kiel, Germany.
Sandra KrügerDepartment of Pathology, General Pathology and Hematopathology, University Hospital Schleswig-Holstein, Kiel, Germany.
Ibrahim AlkatoutDepartment of Gynecology and Obstetrics, University Hospital Schleswig-Holstein, Kiel, Germany.
Antonia WennersDepartment of Gynecology and Obstetrics, University Hospital Schleswig-Holstein, Kiel, Germany.
Maret BauerFrauenpraxis Ostufer, Kiel, Germany.
Wolfram KlapperDepartment of Pathology, General Pathology and Hematopathology, University Hospital Schleswig-Holstein, Kiel, Germany.
Christoph RöckenDepartment of Pathology, General Pathology and Hematopathology, University Hospital Schleswig-Holstein, Kiel, Germany.
Nicolai MaassDepartment of Gynecology and Obstetrics, University Hospital Schleswig-Holstein, Kiel, Germany.
Silvia von KarstedtDepartment of Translational Genomics, University Hospital Cologne, Cologne, Germany.
Christian SchemDepartment of Gynecology and Obstetrics, University Hospital Schleswig-Holstein, Kiel, Germany.
Anna TrauzoldInstitute for Experimental Cancer Research, Christian-Albrechts-University of Kiel, Arnold-Heller Str. 3 (Haus 17), 24105, Kiel, Germany. atrauzold@email.uni-kiel.de.
University Hospital Schleswig-Holstein · DEKiel University · DEUniversity of Lübeck · DEClinical Research Center Kiel · DEUniversity Hospital Cologne · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Upon ligand binding, plasma membrane-located TNF-related apoptosis-inducing ligand (TRAIL)-receptors 1 and 2 induce apoptosis as well as cancer-promoting signaling in cancer cells. TRAIL-R3 and TRAIL-R4 are believed to negatively regulate TRAIL-mediated apoptosis. Intracellular localization of TRAIL-receptors, as observed in many tumor cells, has been associated with oncogenic features, which are distinct from membrane-associated TRAIL-R signaling. Here, analyzing a panel of 354 breast cancer specimens, we found that an unfavorable outcome correlating with cancer-promoting properties of TRAIL-R1, TRAIL-R2, and TRAIL-R4 was most significantly defined by their intracellular distribution and mutual co-expression. A nuclear or cytoplasmic heterogeneous expression pattern correlated with markedly decreased overall survival and discriminated high-risk breast cancer patients from low-risk patients with a homogeneous distribution of expression, i.e., nuclear and cytoplasmic expression. The homogeneous TRAIL-R expression was associated with favorable breast cancer surrogate markers corresponding with excellent survival prognoses at 5 years after diagnosis (hazard ratio, 0.043) and over the complete course of follow-up (hazard ratio, 0.098; both p < 0.001). No associations with specific intrinsic breast cancer subtypes were found. Our data suggest that the determination of intracellular co-expression patterns of TRAIL-R1, TRAIL-R2, and TRAIL-R4 provides an innovative and robust method for risk stratification in breast cancer patients beyond conventional prognostic markers. KEY MESSAGES: A total of 70% of breast cancer specimens show comparably high levels of intracellular TRAIL-Rs. Nuclear or cytoplasmic TRAIL-R co-expression occurs in the majority of tumors. A total of 25% of tumors show a heterogeneous expression of cytoplasmic or nuclear TRAIL-Rs. Patients with a heterogeneous TRAIL-R expression present with poor prognoses. Additive TRAIL-R-based risk stratification comprises different breast cancer subtypes.

Indexed as

Breast NeoplasmsGene Expression Regulation, NeoplasticAgedBiomarkers, TumorDisease-Free SurvivalFemaleHumansMicroRNAsMiddle AgedNeoplasm ProteinsReceptors, TNF-Related Apoptosis-Inducing LigandRetrospective StudiesRNA, NeoplasmSurvival RateTumor Necrosis Factor Decoy ReceptorsBiomarkers, TumorMicroRNAsmirnlet7 microRNA, humanNeoplasm ProteinsReceptors, TNF-Related Apoptosis-Inducing LigandRNA, NeoplasmTNFRSF10A protein, humanTNFRSF10B protein, humanTNFRSF10D protein, humanTumor Necrosis Factor Decoy ReceptorsBreast cancerMolecular markerTRAILTRAIL-receptorTRAIL-receptor interaction

Identifiers

PMID31183506
OpenAlexW2951146007

What OpenQuestion holds

Textmetadata
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 OpenQuestion graph.