Evidence mapPaperPMID 35384413Full record

ArticleThe journal of pathology. Clinical research2022

Homologous recombination deficiency is inversely correlated with microsatellite instability and identifies immunologically cold tumors in most cancer types.

Jan Budczies, Klaus Kluck, Susanne Beck, Iordanis Ourailidis, Michael Allgäuer, Michael Menzel, Daniel Kazdal, Lukas Perkhofer, Alexander Kleger, Peter Schirmacher and 2 more

Open access · goldAbstract read
In one paragraph

Article in The journal of pathology. Clinical research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
3.1field-weighted citation impact, top 7% 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

22 citing papers in PubMed, 32 citations in OpenAlex.

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  3. Prognostic implications of tissue-based homologous recombination deficiency in metastatic gastric cancer treated with immune checkpoint inhibitor plus chemotherapy.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2026
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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

12 authors at 3 institutions in 2 countries.

Jan BudcziesInstitute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.ORCID 0000-0002-6668-5327
Klaus KluckInstitute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Susanne BeckInstitute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Iordanis OurailidisInstitute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Michael AllgäuerInstitute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Michael MenzelInstitute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Daniel KazdalInstitute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.ORCID 0000-0001-8187-3281
Lukas PerkhoferCenters for Personalized Medicine (ZPM), Heidelberg and Ulm Partner Sites, Germany.
Alexander KlegerCenters for Personalized Medicine (ZPM), Heidelberg and Ulm Partner Sites, Germany.
Peter SchirmacherInstitute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Thomas SeufferleinCenters for Personalized Medicine (ZPM), Heidelberg and Ulm Partner Sites, Germany.
Albrecht StenzingerInstitute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Heidelberg University · DECenter for Personalized Cancer Treatment · NLGerman Cancer Research Center · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Homologous recombination deficiency (HRD) leads to DNA double-strand breaks and can be exploited by the use of poly (ADP-ribose) polymerase (PARP) inhibitors to induce synthetic lethality. Extending the original therapeutic concept, the role of HRD is currently being investigated in clinical trials testing immune checkpoint blockers alone or in combination with PARP inhibitors, but the relationship between HRD and immune cell context in cancer is incompletely understood. We analyzed the association between immune cell composition, gene expression, and HRD in 9,041 tumors of 32 solid cancer types from The Cancer Genome Atlas (TCGA). The numbers of genomic scars were quantified by the HRD sum score (HRDsum) including loss of heterozygosity, large-scale state transitions, and telomeric allelic imbalance. The T-cell inflamed gene expression profile correlated weakly, but significantly positively, with HRDsum across cancer types (ρ = 0.17). Within individual cancer types, a significantly positive correlation was observed only in breast cancer, ovarian cancer, and four other cancer types, but not in the remaining 26 cancer types. HRDsum and tumor mutational burden (TMB) correlated significantly positively across cancer types (ρ = 0.42) and within 18 cancer types. HRDsum and a proliferation metagene correlated significantly positively across cancer types (ρ = 0.52) and within 20 cancer types. Mismatch repair deficiency and HRD as well as proofreading deficiency showed a high level of exclusivity. High HRD scores were associated with an immunologically activated tumor microenvironment only in a minority of cancer types. Our data favor the combination of genetic markers, complex genomic markers (including HRDsum and TMB), and other molecular markers (including proliferation scores) for a precise and comprehensive read-out of the tumor biology and an individually tailored treatment.

Indexed as

Microsatellite InstabilityOvarian NeoplasmsBiomarkers, TumorCarcinoma, Ovarian EpithelialFemaleHomologous RecombinationHumansPoly(ADP-ribose) Polymerase InhibitorsTumor MicroenvironmentBiomarkers, TumorPoly(ADP-ribose) Polymerase Inhibitorshomologous recombination deficiencyHRDimmune cell populationsmicrosatellite instabilityMSIPARP inhibitorsT-cell inflamed gene expression profiletumor mutational burden

Identifiers

PMID35384413
PMCPMC9161338
OpenAlexW4225655924

What Socratic holds

Textmetadata
LicenceCC BY-NC
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.