Nuclear factor, erythroid 2-like 2-associated molecular signature predicts lung cancer survival.

TitleNuclear factor, erythroid 2-like 2-associated molecular signature predicts lung cancer survival.
Publication TypeJournal Article
Year of Publication2015
AuthorsQian Z, Zhou T, Gurguis CI, Xu X, Wen Q, Lv J, Fang F, Hecker L, Cress AE, Natarajan V, Jacobson JR, Zhang DD, Garcia JGN, Wang T
JournalSci Rep
Volume5
Pagination16889
Date Published2015 Nov 24
ISSN Number2045-2322
KeywordsAdenocarcinoma, Carcinoma, Squamous Cell, Gene Expression, Humans, Kaplan-Meier Estimate, Lung Neoplasms, NF-E2-Related Factor 2, Prognosis, Proportional Hazards Models, Transcriptome
Abstract

<p>Nuclear factor, erythroid 2-like 2 (NFE2L2), a transcription factor also known as NF-E2-related factor 2 (Nrf2), is a key cytoprotective gene that regulates critical antioxidant and stress-responsive genes. Nrf2 has been demonstrated to be a promising therapeutic target and useful biomarker in malignant disease. We hypothesized that NFE2L2-mediated gene expression would reflect cancer severity and progression. We conducted a meta-analysis of microarray data for 240 NFE2L2-mediated genes that were enriched in tumor tissues. We then developed a risk scoring system based on NFE2L2 gene expression profiling and designated 50 tumor-associated genes as the NFE2L2-associated molecular signature (NAMS). We tested the relationship between this gene expression signature and both recurrence-free survival and overall survival in lung cancer patients. We find that NAMS predicts clinical outcome in the training cohort and in 12 out of 20 validation cohorts. Cox proportional hazard regressions indicate that NAMS is a robust prognostic gene signature, independent of other clinical and pathological factors including patient age, gender, smoking, gene alteration, MYC level, and cancer stage. NAMS is an excellent predictor of recurrence-free survival and overall survival in human lung cancer. This gene signature represents a promising prognostic biomarker in human lung cancer.</p>

DOI10.1038/srep16889
Alternate JournalSci Rep
PubMed ID26596768
PubMed Central IDPMC4657037
Grant ListIK2 BX001477 / BX / BLRD VA / United States
HL91899 / HL / NHLBI NIH HHS / United States
R01 CA154377 / CA / NCI NIH HHS / United States
CA154377 / CA / NCI NIH HHS / United States
HL58064 / HL / NHLBI NIH HHS / United States
P01 HL058064 / HL / NHLBI NIH HHS / United States
R01 HL091889 / HL / NHLBI NIH HHS / United States