title: Nuclear factor, erythroid 2-like 2-associated molecular signature predicts lung cancer survival.
abstract: 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.
authors.affiliation: Key Laboratory of Anhui Province for Infection and Immunology, Bengbu Medical College, Bengbu 233003, China.|Arizona Respiratory Center and Department of Medicine, The University of Arizona, Tucson, Arizona, USA.
authors.forename: Zhongqing
authors.initials: Z
authors.lastname: Qian
authors.affiliation: Arizona Respiratory Center and Department of Medicine, The University of Arizona, Tucson, Arizona, USA.
authors.forename: Tong
authors.initials: T
authors.lastname: Zhou
authors.affiliation: Arizona Respiratory Center and Department of Medicine, The University of Arizona, Tucson, Arizona, USA.
authors.forename: Christopher I
authors.initials: CI
authors.lastname: Gurguis
authors.affiliation: Arizona Respiratory Center and Department of Medicine, The University of Arizona, Tucson, Arizona, USA.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Pharmacy, Jinan Central Hospital, Jinan, Shandong, China.|Department of Pharmacology and Toxicology, The University of Arizona, Tucson, Arizona, USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Wen
authors.affiliation: Department of Biochemistry and Molecular Biology, Bengbu Medical College, Bengbu 233003, China.
authors.forename: Jingzhu
authors.initials: J
authors.lastname: Lv
authors.affiliation: Key Laboratory of Anhui Province for Infection and Immunology, Bengbu Medical College, Bengbu 233003, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Fang
authors.affiliation: Arizona Respiratory Center and Department of Medicine, The University of Arizona, Tucson, Arizona, USA.|Southern Arizona VA Health Care System, Tucson, AZ 85723, USA.
authors.forename: Louise
authors.initials: L
authors.lastname: Hecker
authors.affiliation: Arizona Cancer Center and Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ, USA.
authors.forename: Anne E
authors.initials: AE
authors.lastname: Cress
authors.affiliation: Department of Pharmacology, The University of Illinois at Chicago, Chicago, IL, USA.|Department of Medicine, The University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Viswanathan
authors.initials: V
authors.lastname: Natarajan
authors.affiliation: Department of Medicine, The University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Jacobson
authors.affiliation: Department of Pharmacology and Toxicology, The University of Arizona, Tucson, Arizona, USA.
authors.forename: Donna D
authors.initials: DD
authors.lastname: Zhang
authors.affiliation: Arizona Respiratory Center and Department of Medicine, The University of Arizona, Tucson, Arizona, USA.
authors.forename: Joe G N
authors.initials: JG
authors.lastname: Garcia
authors.affiliation: Arizona Respiratory Center and Department of Medicine, The University of Arizona, Tucson, Arizona, USA.
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D015870:Gene Expression; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D051267:NF-E2-Related Factor 2 / Q000502:physiology*; D011379:Prognosis; D016016:Proportional Hazards Models; D059467:Transcriptome
chemical_list: D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human