Journal
PLOS ONE
Volume 16, Issue 2, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0247020
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Funding
- NSFC cultivation project of Jining Medical University [JYP2019KJ10]
- Medical and Health Science and Technology Development Project of Shandong Province [2019WS357]
- Shanxi Provincial Key Laboratory of Forensic Science, China [SFM2019002]
- Student Innovation Training Program Project of Shandong Province [S202010443043]
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This study found significantly decreased expression of CYP4B1 in patients with LUAD, which was associated with age, treatment history, gene mutations, and survival status. Low CYP4B1 expression was linked to shorter survival time in LUAD patients.
CYP4B1 belongs to the mammalian CYP4 enzyme family and is predominantly expressed in the lungs of humans. It is responsible for the oxidative metabolism of a wide range of endogenous compounds and xenobiotics. In this study, using data from The Cancer Genome Atlas (TCGA) project and the Gene Expression Omnibus (GEO) database, a secondary analysis was performed to explore the expression profile of CYP4B1, as well as its prognostic value in patients with lung adenocarcinoma (LUAD). Based on the obtained results, a significantly decreased CYP4B1 expression was discovered in patients with LUAD when compared with their normal counterparts (p<0.05), and was linked to age younger than 65 years (p = 0.0041), history of pharmaceutical (p = 0.0127) and radiation (p = 0.0340) therapy, mutations in KRAS/EGFR/ALK (p = 0.0239), and living status of dead (p = 0.0026). Survival analysis indicated that the low CYP4B1 expression was an independent prognostic indicator of shorter survival in terms of overall survival (OS) and recurrence-free survival (RFS) in patients with LUAD. The copy number alterations (CNAs) and sites of cg23440155 and cg23414387 hypermethylation might contribute to the decreased CYP4B1 expression. Gene set enrichment analysis (GSEA) suggested that CYP4B1 might act as an oncogene in LUAD by preventing biological metabolism pathways of exogenous and endogenous compounds and enhancing DNA replication and cell cycle activities. In conclusion, CYP4B1 expression may serve as a valuable independent prognostic biomarker and a potential therapeutic target in patients with LUAD.
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