Evidence map›Paper›PMID 21248763›Full record

ArticleJournal of human genetics2011

KEAP1 gene mutations and NRF2 activation are common in pulmonary papillary adenocarcinoma.

Qing Kay Li, Anju Singh, Shyam Biswal, Frederic Askin, Edward Gabrielson

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of human genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed, 1 pooled it
2.7field-weighted citation impact, top 10% 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

57 citing papers in PubMed, 1 synthesis or guideline pooled it, 87 citations in OpenAlex.

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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

5 authors at 2 institutions in 1 country.

Qing Kay LiDepartment of Pathology, The Johns Hopkins School of Medicine, Johns Hopkins University, Baltimore, MD 21287, USA. qli23@jhmi.edu
Anju Singh
Shyam Biswal
Frederic Askin
Edward Gabrielson
Johns Hopkins University · USJohns Hopkins Medicine · US

Funding

TARGETING EARLY CHANGES FOR NEW SCREENING STRATEGIESP50CA058184 · NCI · JOHNS HOPKINS UNIVERSITY · PI BISWAL, SHYAM · 1992 to 2013
$30.5M
Regulation of Tumorigenesis and therapeutic resistance by Nrf2 in lung cancerR01CA140492 · NCI · JOHNS HOPKINS UNIVERSITY · PI BISWAL, SHYAM · 2010 to 2014
$1.8M
NCI NIH HHS P50 CA058184NCI NIH HHS R01 CA140492
6 · The paper itself

Abstract

Distinctive histological variants of lung cancer are increasingly recognized to have specific genetic changes that affect tumor biology and response to therapy. In this study, we evaluated true papillary adenocarcinoma of the lung, proposed as a distinct diagnostic category with relatively poor response to therapy, to determine whether these tumors also have specific molecular alterations that would affect sensitivity to chemotherapy. Specifically, we measured protein levels of P53, excision repair cross-complementation 1 (ERCC1) and ribonucleotide reductase M1 (RRM1) by immunohistochemistry and evaluated the Kelch-like erythroid cell-derived protein with cap-n-collar homology (ECH)-associated protein 1 (KEAP1) gene for mutations, correlating mutations of this gene with total and nuclear expression of the nuclear factor erythroid-2-related factor 2 (NRF2). We found high levels of P53 in 23 of the 55 specimens (41.8%), similar to the rate of P53 gene mutations observed in general for pulmonary adenocarcinoma, and levels of ERCC1 and RRM1 also showed distributions similar to those reported generally for non-small lung cell cancer (NSCLC). However, KEAP1 alterations were observed at a significantly higher frequency in papillary adenocarcinoma tumors (60%) than what has been reported previously for NSCLC (3-19%). These mutations of KEAP1 were associated with increased nuclear accumulation of NRF2 in tumors, as expected for functional alterations. Thus, high rates of KEAP1 mutations and NRF2 overexpression in true papillary adenocarcinoma could be related to poor prognosis and chemotherapy resistance. Furthermore, this distinctive molecular characteristic supports the recognition of true papillary adenocarcinoma as a diagnostic entity.

Indexed as

Adenocarcinoma, PapillaryBase SequenceDNA-Binding ProteinsEndonucleasesHumansIntracellular Signaling Peptides and ProteinsKelch-Like ECH-Associated Protein 1Lung NeoplasmsMutationNF-E2-Related Factor 2Ribonucleoside Diphosphate ReductaseTranscriptional ActivationTumor Suppressor Protein p53Tumor Suppressor ProteinsDNA-Binding ProteinsEndonucleasesERCC1 protein, humanIntracellular Signaling Peptides and ProteinsKEAP1 protein, humanKelch-Like ECH-Associated Protein 1NFE2L2 protein, humanNF-E2-Related Factor 2Ribonucleoside Diphosphate ReductaseRRM1 protein, humanTumor Suppressor Protein p53Tumor Suppressor Proteins

Identifiers

PMID21248763
PMCPMC3268659
OpenAlexW2058493148

What OpenQuestion holds

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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.