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

Liu, Xiaoling; Jia, Yichen; Shi, Changyuan; Kong, Dechen; Wu, Yuan-Ming; Zhang, Tiantian; Wei, Anjie; Wang, Dan

doi:10.1371/journal.pone.0247020

Cited by 23 publications

(25 citation statements)

References 30 publications

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“…CYP4B1 is a member of the CYP4B subfamily, and the current researches on CYP4B1 gene mainly focus on its function analysis. Studies have shown that CYP4B1 plays an important role in the metabolic process of endogenous compounds and exogenous substances (drugs, environmental toxicants, pro-carcinogens), thereby affecting the occurrence and development of diseases [15]. It is well known that the drug metabolizing enzymes in the human body are also the metabolic enzymes of important carcinogens, which control and affect the metabolism of carcinogens, so they play a decisive role in tumor susceptibility.…”

Section: Discussionmentioning

confidence: 99%

Case-control study on CYP4B1 gene polymorphism and susceptibility to gastric cancer in the chinese Han population

Chen

Cheng

et al. 2022

BMC Med Genomics

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Background: In China, gastric cancer (GC) is one of the most common malignant tumors. This study aimed to explore the relationship of rs2297810, rs4646491 and rs2297809 polymorphisms of CYP4B1 with susceptibility to GC in the Chinese Han population. Methods: A case-control study including 707 GC cases and 707 normal controls was conducted. Three single nucleotide polymorphisms (SNPs) were genotyped by Agena MassARRAY system. Logistic regression analysis was utilized to assess the effects of SNPs on GC risk. Furthermore, multifactor dimensionality reduction (MDR) approach was used to analyze the SNP-SNP interactions. Results: No significant relationships were found between rs2297810 and rs2297809 and GC risk under all genetic models. For rs4646491, people with TC genotype had a 1.40-fold higher risk of GC than those with CC genotype (OR = 1.40; 95% CI = 1.13–1.74; p = 0.002), and people with TT-TC genotype had a 1.30-fold higher risk of GC than those with CC genotype (OR = 1.30; 95% CI = 1.06–1.61; p = 0.014). Stratification results showed that GC risk in people carrying TC genotype was higher than that in people with CC genotype, males (OR = 1.36; 95% CI = 1.06–1.75; p = 0.015), non-smokers (OR = 1.52; 95% CI = 1.11–2.07; p = 0.009) and non-drinkers (OR = 1.50; 95% CI = 1.10–2.04; p = 0.010). Additionally, the study also revealed that GC risk in people carrying TT-TC genotype was higher than that in people with CC genotype, males (OR = 1.29; 95% CI = 1.01–1.64; p = 0.040), non-smokers (OR = 1.40; 95% CI = 1.04–1.89; p = 0.027) and non-drinkers (OR = 1.39; 95% CI = 1.03–1.87; p = 0.030). Conclusion: This study firstly found that CYP4B1-rs4646491 was significantly correlated with GC risk, and it might be a risk factor for GC.

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Section: Discussionmentioning

confidence: 99%

Case-control study on CYP4B1 gene polymorphism and susceptibility to gastric cancer in the chinese Han population

Chen

Cheng

et al. 2022

BMC Med Genomics

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“…CYP4B1 is a member of the cytochrome P450 superfamily of monooxygenases that catalyze drug metabolism and synthesis of cholesterol, steroids, and other lipids [ 21 ]. Studies have uncovered the role of CYP4B1 in the oxidation of fatty acids, activation of procarcinogens and neovascularization, and the promising potential as a target in cancer treatment [ 22 , 23 ]. PLK1 is a Serine/Threonine protein kinase of the CDC5/Polo subfamily and a critical cell cycle regulator frequently overexpressed in cancers [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

A Metabolism-Related Gene Prognostic Index for Prediction of Response to Immunotherapy in Lung Adenocarcinoma

Tang

Jiang

et al. 2022

IJMS

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Immunotherapy, such as immune checkpoint inhibitors (ICIs), is a validated strategy for treating lung adenocarcinoma (LUAD) patients. One of the main challenges in ICIs treatment is the lack of efficient biomarkers for predicting response or resistance. Metabolic reprogramming has been proven to remodel the tumor microenvironment, altering the response to ICIs. We constructed a prognostic model as metabolism-related gene (MRG) of four genes by using weighted gene co-expression network analysis (WGCNA), the nonnegative matrix factorization (NMF), and Cox regression analysis of a LUAD dataset (n = 500) from The Cancer Genome Atlas (TCGA), which was validated with three Gene Expression Omnibus (GEO) datasets (n = 442, n = 226 and n = 127). The MRG was constructed based on BIRC5, PLK1, CDKN3, and CYP4B1 genes. MRG-high patients had a worse survival probability than MRG-low patients. Furthermore, the MRG-high subgroup was more associated with cell cycle-related pathways; high infiltration of activated memory CD4+T cells, M0 macrophages, and neutrophils; and showed better response to ICIs. Contrarily, the MRG-low subgroup was associated with fatty acid metabolism, high infiltration of dendric cells, and resting mast cells, and showed poor response to ICIs. MRG is a promising prognostic index for predicting survival and response to ICIs and other therapeutic agents in LUAD, which might provide insights on strategies with ICIs alone or combined with other agents.

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“…The loss of CYP4B1 gene expression is related to bladder urothelial carcinoma (51), and its low expression is related to the poor prognosis of LUAD patients. Therefore, it can be used as an independent prognostic marker and a potential therapeutic target for patients with LUAD (52).…”

Section: Discussionmentioning

confidence: 99%

Analysis of prognostic model based on immunotherapy related genes in lung adenocarcinoma

Zhang

Wang

Liu

et al. 2022

Preprint

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Lung cancer is one of the most common malignant tumors, and ranks high in the list of mortality due to cancers. Lung adenocarcinoma(LUAD) is the most common subtype of lung cancer. Despite progress in the diagnosis and treatment of lung cancer, the prognosis of these patients remains dismal. Therefore, it is crucial to identify the predictors and treatment targets of lung cancer to provide appropriate treatments and improve patient prognosis. In this study, the gene modules related to immunotherapy were screened by weighted gene co-expression network analysis (WGCNA). Using unsupervised clustering, patients in The Cancer Genome Atlas (TCGA) were divided into three clusters based on the gene expression. Next, gene clustering was performed on the prognosis-related differential genes, and a six-gene prognosis model (comprising PLK1, HMMR, ANLN, SLC2A1, SFTPB, and CYP4B1) was constructed using least absolute shrinkage and selection operator (LASSO) analysis. Patients with LUAD were divided into two groups: high-risk and low-risk. Significant differences were found in the survival, immune cell infiltration,Tumor mutational burden (TMB), immune checkpoints, and immune microenvironment between the high- and low-risk groups. Finally, the accuracy of the prognostic model was verified in the Gene Expression Omnibus（GEO） dataset in patients with LUAD (GSE30219、GSE31210、GSE50081、GSE72094).

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

Cited by 23 publications

References 30 publications

Case-control study on CYP4B1 gene polymorphism and susceptibility to gastric cancer in the chinese Han population

Case-control study on CYP4B1 gene polymorphism and susceptibility to gastric cancer in the chinese Han population

A Metabolism-Related Gene Prognostic Index for Prediction of Response to Immunotherapy in Lung Adenocarcinoma

Analysis of prognostic model based on immunotherapy related genes in lung adenocarcinoma

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