Evidence map›Paper›PMID 33805812›Full record

ArticleCancers2021

Development of a Novel Weighted Ranking Method for Immunohistochemical Quantification of a Heterogeneously Expressed Protein in Gastro-Esophageal Cancers.

Cathy E Richards, Katherine M Sheehan, Elaine W Kay, Charlotta Hedner, David Borg, Joanna Fay, Anthony O'Grady, Arnold D K Hill, Karin Jirström, Ann M Hopkins

Open access · goldAbstract read
In one paragraph

Article in Cancers, 2021. 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
0.1field-weighted citation impact, top 57% 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, 1 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

10 authors at 2 institutions in 2 countries.

Cathy E RichardsDepartment of Surgery, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin 9, Ireland.ORCID 0000-0002-6551-8017
Katherine M SheehanDepartment of Pathology, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin 9, Ireland.
Elaine W KayDepartment of Pathology, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin 9, Ireland.
Charlotta HednerDepartment of Clinical Sciences Lund, Division of Oncology and Therapeutic Pathology, Lund University, SE 221 85 Lund, Sweden.
David BorgDepartment of Clinical Sciences Lund, Division of Oncology and Therapeutic Pathology, Lund University, SE 221 85 Lund, Sweden.ORCID 0000-0001-9461-7391
Joanna FayDepartment of Pathology, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin 9, Ireland.ORCID 0000-0001-6294-2886
Anthony O'GradyDepartment of Pathology, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin 9, Ireland.
Arnold D K HillDepartment of Surgery, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin 9, Ireland.
Karin JirströmDepartment of Clinical Sciences Lund, Division of Oncology and Therapeutic Pathology, Lund University, SE 221 85 Lund, Sweden.
Ann M HopkinsDepartment of Surgery, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin 9, Ireland.ORCID 0000-0003-2836-6584
Royal College of Surgeons in Ireland · IELund University · SE

Funding

Breast Cancer Ireland 2019Science Foundation Ireland 13/IA/1994
6 · The paper itself

Abstract

High expression of Junctional Adhesion Molecule-A (JAM-A) has been linked with poor prognosis in several cancers, including breast cancers overexpressing the human epidermal growth factor receptor-2 (HER2). Furthermore, JAM-A expression has been linked with regulating that of HER2, and associated with the development of resistance to HER2-targeted therapies in breast cancer patients. The purpose of this study was to establish a potential relationship between JAM-A and HER2 in HER2-overexpressing gastro-esophageal (GE) cancers. Interrogation of gene expression datasets revealed that high JAM-A mRNA expression was associated with poorer survival in HER2-positive gastric cancer patients. However, high intra-tumoral heterogeneity of JAM-A protein expression was noted upon immunohistochemical scoring of a GE cancer tissue microarray (TMA), precluding a simple confirmation of any relationship between JAM-A and HER2 at protein level. However, in a test-set of 25 full-face GE cancer tissue sections, a novel weighted ranking system proved effective in capturing JAM-A intra-tumoral heterogeneity and confirming statistically significant correlations between JAM-A/HER2 expression. Given the growing importance of immunohistochemistry in stratifying cancer patients for the receipt of new targeted therapies, this may sound a cautionary note against over-relying on cancer TMAs in biomarker discovery studies of heterogeneously expressed proteins. It also highlights a timely need to develop validated mechanisms of capturing intra-tumoral heterogeneity to aid in future biomarker/therapeutic target development for the benefit of cancer patients.

Indexed as

cancergastro-esophageal cancerHER2immunohistochemistryintra-tumoral heterogeneityJAM-Atissue microarraytumor

Identifiers

PMID33805812
PMCPMC7998246
OpenAlexW3137223394

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.