Evidence map›Paper›PMID 36980544›Full record

ArticleCancers2023

A Novel Subgroup of UCHL1-Related Cancers Is Associated with Genomic Instability and Sensitivity to DNA-Damaging Treatment.

Sebastian Burkart, Christopher Weusthof, Karam Khorani, Sonja Steen, Fabian Stögbauer, Kristian Unger, Julia Hess, Horst Zitzelsberger, Claus Belka, Ina Kurth and 1 more

Open access · goldAbstract read
In one paragraph

Article in Cancers, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.5field-weighted citation impact, top 34% 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

2 citing papers in PubMed, 3 citations in OpenAlex.

  1. Review
  2. 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

11 authors at 3 institutions in 1 country.

Sebastian BurkartSection Experimental and Translational Head and Neck Oncology, Department of Otolaryngology, Head and Neck Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany.ORCID 0000-0002-4135-066X
Christopher WeusthofSection Experimental and Translational Head and Neck Oncology, Department of Otolaryngology, Head and Neck Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany.
Karam KhoraniSection Experimental and Translational Head and Neck Oncology, Department of Otolaryngology, Head and Neck Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany.
Sonja SteenDepartment of Oral and Maxillofacial Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany.
Fabian StögbauerTissue Bank of the National Center for Tumor Diseases (NCT), Institute of Pathology, University Hospital Heidelberg, 69120 Heidelberg, Germany.ORCID 0000-0002-8897-5165
Kristian UngerResearch Unit Radiation Cytogenetics, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, 85764 Neuherberg, Germany.
Julia HessResearch Unit Radiation Cytogenetics, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, 85764 Neuherberg, Germany.ORCID 0000-0001-9860-1426
Horst ZitzelsbergerResearch Unit Radiation Cytogenetics, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, 85764 Neuherberg, Germany.
Claus BelkaClinical Cooperation Group Personalized Radiotherapy in Head and Neck Cancer, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, 85764 Neuherberg, Germany.
Ina KurthDivision of Radiooncology-Radiobiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.ORCID 0000-0001-9261-5165
Jochen HessSection Experimental and Translational Head and Neck Oncology, Department of Otolaryngology, Head and Neck Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany.ORCID 0000-0003-3493-1711
German Cancer Research Center · DEHeidelberg University · DEHelmholtz Zentrum München · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeIdentification of molecularly-defined cancer subgroups and targeting tumor-specific vulnerabilities have a strong potential to improve treatment response and patient outcomes but remain an unmet challenge of high clinical relevance, especially in head and neck squamous cell carcinoma (HNSC). EXPERIMENTAL

designWe established a UCHL1-related gene set to identify and molecularly characterize a UCHL1-related subgroup within TCGA-HNSC by integrative analysis of multi-omics data. An extreme gradient boosting model was trained on TCGA-HNSC based on GSVA scores for gene sets of the MSigDB to robustly predict UCHL1-related cancers in other solid tumors and cancer cell lines derived thereof. Potential vulnerabilities of UCHL1-related cancer cells were elucidated by an in-silico drug screening approach.

resultsWe established a 497-gene set, which stratified the TCGA-HNSC cohort into distinct subgroups with a UCHL1-related or other phenotype. UCHL1-related HNSC were characterized by higher frequencies of genomic alterations, which was also evident for UCHL1-related cancers of other solid tumors predicted by the classification model. These data indicated an impaired maintenance of genomic integrity and vulnerability for DNA-damaging treatment, which was supported by a favorable prognosis of UCHL1-related tumors after radiotherapy, and a higher sensitivity of UCHL1-related cancer cells to irradiation or DNA-damaging compounds (e.g., Oxaliplatin).

conclusionOur study established UCHL1-related cancers as a novel subgroup across most solid tumor entities with a unique molecular phenotype and DNA-damaging treatment as a specific vulnerability, which requires further proof-of-concept in pre-clinical models and future clinical trials.

Indexed as

head and neck squamous cell carcinoma (HNSCHNSCC)integrative multi-omics analysispan-cancerradiotherapyubiquitin C-terminal hydrolase L1

Identifiers

PMID36980544
PMCPMC10099714
OpenAlexW4323569184

What OpenQuestion holds

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Registered trials

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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.