CYP4B1 is a prognostic biomarker and potential therapeutic target in lung adenocarcinoma

PLoS One. 2021 Feb 16;16(2):e0247020. doi: 10.1371/journal.pone.0247020. eCollection 2021.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma of Lung / diagnosis
  • Adenocarcinoma of Lung / drug therapy*
  • Adenocarcinoma of Lung / genetics
  • Adenocarcinoma of Lung / metabolism*
  • Aged
  • Aryl Hydrocarbon Hydroxylases / genetics
  • Aryl Hydrocarbon Hydroxylases / metabolism*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Middle Aged
  • Molecular Targeted Therapy*
  • Prognosis

Substances

  • Biomarkers, Tumor
  • Aryl Hydrocarbon Hydroxylases
  • cytochrome P-450 CYP4B1

Grants and funding

This study was supported by the NSFC cultivation project of Jining Medical University (JYP2019KJ10), the Medical and Health Science and Technology Development Project of Shandong Province (2019WS357), the open project of Shanxi Provincial Key Laboratory of Forensic Science, China (SFM2019002) and the Student Innovation Training Program Project of Shandong Province (S202010443043). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.