Evidence map›Paper›PMID 40537696›Full record

ArticleGeroScience2026

NRF2 pathway activation predicts poor prognosis in lung cancer: a cautionary note on antioxidant interventions.

Zoltan Ungvari, Otília Menyhart, Andrea Lehoczki, Monika Fekete, Vince Fazekas-Pongor, Alberto Ocana, Peter Varga, Balázs Győrffy

Abstract read
In one paragraph

Article in GeroScience, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. 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

8 authors.

Zoltan Ungvari *Vascular Cognitive Impairment, Neurodegeneration and Healthy Brain Aging Program, Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Otília Menyhart *Cancer Biomarker Research Group, Institute of Molecular Life Sciences, Hungarian Research Network, Magyar Tudósok Körútja 2, Budapest, 1117, Hungary.
Andrea Lehoczki *Doctoral College, Health Sciences Division, Semmelweis University, Budapest, Hungary. Andrea.M.Lehoczki@gmail.com.ORCID 0000-0002-4285-7518
Monika FeketeInstitute of Preventive Medicine and Public Health, Semmelweis University, Budapest, Hungary.
Vince Fazekas-PongorInstitute of Preventive Medicine and Public Health, Semmelweis University, Budapest, Hungary.
Alberto OcanaExperimental Therapeutics in Cancer Unit, Instituto de Investigación Sanitaria San Carlos (IdISSC), and CIBERONC, Madrid, Spain.
Peter VargaInstitute of Preventive Medicine and Public Health, Semmelweis University, Budapest, Hungary.
Balázs GyőrffyCancer Biomarker Research Group, Institute of Molecular Life Sciences, Hungarian Research Network, Magyar Tudósok Körútja 2, Budapest, 1117, Hungary.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Lung cancer is a leading cause of cancer-related mortality worldwide. As an age-related disease, its pathogenesis is shaped by several molecular hallmarks of aging, including impaired DNA repair and diminished stress resilience. The transcription factor NRF2 (nuclear factor erythroid 2-related factor 2) is a master regulator of oxidative stress defense and cellular survival. While NRF2 activation is protective in aging tissues, it may also be exploited by cancer cells to promote tumor progression and therapy resistance. This study aims to evaluate whether NRF2 pathway activation predicts clinical outcomes in lung cancer, with potential implications for the use of NRF2-inducing compounds. We analyzed transcriptomic and survival data from 2167 lung cancer patients using the KM Plotter database. A validated 14-gene NRF2 activation signature was used to stratify tumors by NRF2 pathway activity. Associations with overall survival (OS), first progression (FP), and post-progression survival (PPS) were assessed using Cox regression models and Kaplan-Meier analysis. High NRF2 signature expression was significantly associated with poorer OS (HR = 1.59, p = 1.3E-9), FP (HR = 1.61, p = 2.6E-5), and PPS (HR = 1.6, p = 0.002). The negative prognostic effect was most pronounced in patients with adenocarcinoma, node-negative disease, and in female patients. These findings highlight the dual role of NRF2 in promoting stress resilience and enabling cancer cell survival. NRF2 activation is a predictor of poor clinical outcomes in lung cancer. Given the widespread use of NRF2-inducing compounds such as resveratrol and sulforaphane, these findings raise important concerns about their safety in individuals at risk for or living with cancer. Our results underscore the importance of context-specific evaluation of NRF2-targeted interventions and caution against the indiscriminate use of NRF2-activating agents in aging populations, particularly in individuals at risk for lung cancer.

Indexed as

AntioxidantsLung NeoplasmsNF-E2-Related Factor 2AgedFemaleHumansIsothiocyanatesMaleMiddle AgedOxidative StressPrognosisSignal TransductionSulfoxidesAntioxidantsIsothiocyanatesNFE2L2 protein, humanNF-E2-Related Factor 2sulforaphaneSulfoxidesAgingAging-related diseaseAntioxidantsCancer biomarkersCancer preventionDietary supplementsGene expression signatureKEAP1Lung cancerNon-small cell lung cancerNutraceuticalsOxidative stressPrognosisPrognostic biomarkersRedox biologyRedox signalingResveratrolStress resilienceSystems biologyTherapy resistanceTranscriptomics

Identifiers

PMID40537696
PMCPMC12972416

What Socratic 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 Socratic graph.