Evidence map›Paper›PMID 29306329›Full record

ArticleBMC cancer2018

Gene-expression signature regulated by the KEAP1-NRF2-CUL3 axis is associated with a poor prognosis in head and neck squamous cell cancer.

Akhileshwar Namani, Md Matiur Rahaman, Ming Chen, Xiuwen Tang

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

Article in BMC cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed
5.3field-weighted citation impact, top 3% 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

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3 · Its place in the literature

Who cites it

62 citing papers in PubMed, 117 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

4 authors at 1 institution in 1 country.

Akhileshwar NamaniDepartment of Biochemistry, University School of Medicine, Hangzhou, 310058, People's Republic of China.
Md Matiur RahamanDepartment of Bioinformatics, College of Life Sciences, Zhejiang University, Hangzhou, 310058, People's Republic of China.
Ming ChenDepartment of Bioinformatics, College of Life Sciences, Zhejiang University, Hangzhou, 310058, People's Republic of China. mchen@zju.edu.cn.
Xiuwen TangDepartment of Biochemistry, University School of Medicine, Hangzhou, 310058, People's Republic of China. xiuwentang@zju.edu.cn.ORCID 0000-0002-6601-1234
Zhejiang University · CN

Funding

The National Natural Sciences Foundation of china 31170743,81172230
6 · The paper itself

Abstract

backgroundNRF2 is the key regulator of oxidative stress in normal cells and aberrant expression of the NRF2 pathway due to genetic alterations in the KEAP1 (Kelch-like ECH-associated protein 1)-NRF2 (nuclear factor erythroid 2 like 2)-CUL3 (cullin 3) axis leads to tumorigenesis and drug resistance in many cancers including head and neck squamous cell cancer (HNSCC). The main goal of this study was to identify specific genes regulated by the KEAP1-NRF2-CUL3 axis in HNSCC patients, to assess the prognostic value of this gene signature in different cohorts, and to reveal potential biomarkers.

methodsRNA-Seq V2 level 3 data from 279 tumor samples along with 37 adjacent normal samples from patients enrolled in the The Cancer Genome Atlas (TCGA)-HNSCC study were used to identify upregulated genes using two methods (altered KEAP1-NRF2-CUL3 versus normal, and altered KEAP1-NRF2-CUL3 versus wild-type). We then used a new approach to identify the combined gene signature by integrating both datasets and subsequently tested this signature in 4 independent HNSCC datasets to assess its prognostic value. In addition, functional annotation using the DAVID v6.8 database and protein-protein interaction (PPI) analysis using the STRING v10 database were performed on the signature.

resultsA signature composed of a subset of 17 genes regulated by the KEAP1-NRF2-CUL3 axis was identified by overlapping both the upregulated genes of altered versus normal (251 genes) and altered versus wild-type (25 genes) datasets. We showed that increased expression was significantly associated with poor survival in 4 independent HNSCC datasets, including the TCGA-HNSCC dataset. Furthermore, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and PPI analysis revealed that most of the genes in this signature are associated with drug metabolism and glutathione metabolic pathways.

conclusionsAltogether, our study emphasizes the discovery of a gene signature regulated by the KEAP1-NRF2-CUL3 axis which is strongly associated with tumorigenesis and drug resistance in HNSCC. This 17-gene signature provides potential biomarkers and therapeutic targets for HNSCC cases in which the NRF2 pathway is activated.

Indexed as

Biomarkers, TumorCarcinogenesisCarcinoma, Squamous CellCullin ProteinsDrug Resistance, NeoplasmFemaleGene Expression Regulation, NeoplasticHead and Neck NeoplasmsHigh-Throughput Nucleotide SequencingHumansKelch-Like ECH-Associated Protein 1MaleMutationNF-E2-Related Factor 2PrognosisSignal TransductionBiomarkers, TumorCUL3 protein, humanCullin ProteinsKEAP1 protein, humanKelch-Like ECH-Associated Protein 1NFE2L2 protein, humanNF-E2-Related Factor 2Gene-expression signatureHead and neck squamous cell cancerKEAP1-NRF2-CUL3 mutationsOverall survival

Identifiers

PMID29306329
PMCPMC5756380
OpenAlexW2782338377

What OpenQuestion holds

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LicenceCC BY
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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.