Evidence map›Paper›PMID 33972574›Full record

ArticleScientific reports2021

Validation of a DKK1 RNAscope chromogenic in situ hybridization assay for gastric and gastroesophageal junction adenocarcinoma tumors.

Charles Caldwell, James B Rottman, Will Paces, Elizabeth Bueche, Sofia Reitsma, Joseph Gibb, Vitria Adisetiyo, Michael S Haas, Heidi Heath, Walter Newman and 3 more

Open access · goldAbstract readValidation Study
In one paragraph

Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.0field-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

11 citing papers in PubMed, 14 citations in OpenAlex.

  1. Trial
  2. Trial
  3. Article
  4. Correlation of TRPA1 RNAscope and Agonist Responses.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2024
    Article
  5. Article
  6. ChromogenicNon-coding RNA research · 2024
    Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. 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

13 authors at 1 institution in 1 country.

Charles CaldwellFlagship Biosciences, Westminster, CO, USA.
James B RottmanAthenaeum Pathology Consulting, Sudbury, MA, USA.
Will PacesFlagship Biosciences, Westminster, CO, USA.
Elizabeth BuecheFlagship Biosciences, Westminster, CO, USA.
Sofia ReitsmaFlagship Biosciences, Westminster, CO, USA.
Joseph GibbFlagship Biosciences, Westminster, CO, USA.
Vitria AdisetiyoFlagship Biosciences, Westminster, CO, USA.
Michael S HaasLeap Therapeutics Inc., 47 Thorndike Street, Suite B1-1, Cambridge, MA, 02141, USA.
Heidi HeathLeap Therapeutics Inc., 47 Thorndike Street, Suite B1-1, Cambridge, MA, 02141, USA.
Walter NewmanLeap Therapeutics Inc., 47 Thorndike Street, Suite B1-1, Cambridge, MA, 02141, USA.
Jason BaumLeap Therapeutics Inc., 47 Thorndike Street, Suite B1-1, Cambridge, MA, 02141, USA.
Roberto GiananiFlagship Biosciences, Westminster, CO, USA.
Michael H KageyLeap Therapeutics Inc., 47 Thorndike Street, Suite B1-1, Cambridge, MA, 02141, USA. mkagey@leaptx.com.
Sage Therapeutics (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Dickkopf-1 (DKK1) is a secreted modulator of Wnt signaling that is frequently overexpressed in tumors and associated with poor clinical outcomes. DKN-01 is a humanized monoclonal therapeutic antibody that binds DKK1 with high affinity and has demonstrated clinical activity in gastric/gastroesophageal junction (G/GEJ) patients with elevated tumoral expression of DKK1. Here we report on the validation of a DKK1 RNAscope chromogenic in situ hybridization assay to assess DKK1 expression in G/GEJ tumor tissue. To reduce pathologist time, potential pathologist variability from manual scoring and support pathologist decision making, a digital image analysis algorithm that identifies tumor cells and quantifies the DKK1 signal was developed. Following CLIA guidelines the DKK1 RNAscope chromogenic in situ hybridization assay and digital image analysis algorithm were successfully validated for sensitivity, specificity, accuracy, and precision. The DKK1 RNAscope assay in conjunction with the digital image analysis solution is acceptable for prospective screening of G/GEJ adenocarcinoma patients. The work described here will further advance the companion diagnostic development of our DKK1 RNAscope assay and could generally be used as a guide for the validation of RNAscope assays with digital image quantification.

Indexed as

AdenocarcinomaAdultAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorCell Line, TumorClinical Trials, Phase II as TopicEsophageal NeoplasmsEsophagogastric JunctionFemaleGene Expression Regulation, NeoplasticHumansImage Processing, Computer-AssistedIn Situ HybridizationIntercellular Signaling Peptides and ProteinsMaleMiddle AgedBiomarkers, TumorDKK1 protein, humanIntercellular Signaling Peptides and ProteinsRNA, Messenger

Identifiers

PMID33972574
PMCPMC8110580
OpenAlexW3161255917

What OpenQuestion holds

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LicenceCC BY
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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.