Ferroptosis-Related Genes in Lung Adenocarcinoma: Prognostic Signature and Immune, Drug Resistance, Mutation Analysis

Ren, Ziyuan; Hu, Minghui; Wang, Zhong Lin; Ge, Junpeng; Zhou, Xiaoyan; Zhang, Guoming; Zheng, Hongying

doi:10.3389/fgene.2021.672904

Cited by 59 publications

(38 citation statements)

References 101 publications

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“…It is also associated with immune cell inflammation (31). Consistently, a very recent study also suggested that increased expression of PEBP1 is related to survival status in lung adenocarcinoma patients (32). In our study, however, only LPIN1 is found to be correlated with survival status in sepsis.…”

Section: Discussionsupporting

confidence: 86%

LPIN1 Is a Regulatory Factor Associated With Immune Response and Inflammation in Sepsis

et al. 2022

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ObjectivesSepsis is a clinical disease that is typically treated in the intensive care unit, and the complex pathophysiology under this disease has not been thoroughly understood. While ferroptosis is involved in inflammation and infection, its effect in sepsis is still unknown. The study aimed to identify ferroptosis-related genes in sepsis, providing translational potential therapeutic targets.MethodsThe dataset GSE65682 was used to download the sample source from the Gene Expression Omnibus (GEO) database. Consensus weighted gene co-expression network analysis (WGCNA) was performed to find suspected modules of sepsis. The differentially expressed genes (DEGs) most significantly associated with mortality were intersected with those altered by lipopolysaccharide (LPS) treatment and were further analyzed for the identification of main pathways of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The related pathway markers were further verified by qPCR.ResultsA total of 802 blood samples with sepsis were included for WGCNA, which identified 21 modules. Intersected with ferroptosis databases and LPS treatment groups, we identified two ferroptosis-related genes: PEBP1 and LPIN1. Only LPIN1 contributes to a poor outcome. Then, 205 DEGs were further identified according to the high or low LPIN1 expression. Among them, we constructed a gene regulatory network with several transcriptional factors using the NetworkAnalyst online tool and identified that these genes mostly correlate with inflammation and immune response. The immune infiltration analysis showed that lower expression of LPIN1 was related to macrophage infiltration and could be an independent predictor factor of the survival status in sepsis patients. Meanwhile, the multivariate Cox analysis showed that LPIN1 had a significant correlation with survival that was further verified by in vitro and in vivo experiments.ConclusionIn conclusion, LPIN1 could become a reliable biomarker for patient survival in sepsis, which is associated with immune and inflammation status.

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Section: Discussionsupporting

confidence: 86%

LPIN1 Is a Regulatory Factor Associated With Immune Response and Inflammation in Sepsis

et al. 2022

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“…When SystemXc- is blocked, glutamate and cystine cannot be exchanged, resulting in intracellular glutamate accumulation, reduced glutathione synthesis, and reduced GPX4 activity, which ultimately leads to ferroptosis ( 58 ). Further, the inhibition of SLC3A2, a ferroptosis suppressor gene, promotes ferroptosis in tumor and normal cells ( 57 , 59 ), and hence, its upregulation is associated with poor prognosis of cancer ( 60 ). FTH1 (Ferritin heavy polypeptide 1) is an important component of ferritin.…”

Section: Discussionmentioning

confidence: 99%

Eucommia ulmoides Oliver-Tribulus terrestris L. Drug Pair Regulates Ferroptosis by Mediating the Neurovascular-Related Ligand-Receptor Interaction Pathway- A Potential Drug Pair for Treatment Hypertension and Prevention Ischemic Stroke

Zhang

Yang

et al. 2022

Front. Neurol.

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BackgroundIn this study, we used the network pharmacology approach to explore the potential disease targets of the Eucommia ulmoides Oliver (EUO)-Tribulus terrestris L. (TT) drug pair in the treatment of hypertension-associated neurovascular lesions and IS via the ferroptosis pathway.MethodsWe used the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform to search for the key active compounds and targets of the drug pair. Based on the GeneCards database, the relevant targets for the drug pair were obtained. Then, we performed the molecular docking of the screened core active ingredients and proteins using the DAVID database and the R AutoDock Vina software. Based on the GSE22255 dataset, these screened target proteins were used to build random forest (RF) and support vector machine (SVM) models. Finally, a new IS nomogram prediction model was constructed and evaluated.ResultsThere were 36 active compounds in the EUO-TT drug pair. CHRM1, NR3C1, ADRB2, and OPRD1 proteins of the neuroactive ligand-receptor interaction pathway interacted with the proteins related to the ferroptosis pathway. Molecular docking experiments identified 12 active ingredients of the drug pair that may tightly bind to those target proteins. We constructed a visual IS nomogram prediction model using four genes (CHRM1, NR3C1, ADRB2, and OPRD1). The calibration curve, DCA, and clinical impact curves all indicated that the nomogram model is clinically applicable and diagnostically capable. CHRM1, NR3C1, ADRB2, and OPRD1, the target genes of the four effective components of the EUO-TT drug pair, were considered as risk markers for IS.ConclusionsThe active ingredients of EUO-TT drug pair may act on proteins associated with the neuroactive ligand-receptor interaction pathway to regulate ferroptosis in vascular neurons cells, ultimately affecting the onset and progression of hypertension.

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“… 44 The proportion of T cells decreased in the lungs of current smokers and patients with COPD, whereas the proportion of macrophages increased. 45 In our study, we uncovered the immune infiltration status in patients with COPD compared with normal controls. Monocytes were the majority of immune cells in both groups and increased prominently in COPD group.…”

Section: Discussionmentioning

confidence: 99%

Identification of Ferroptosis-Related Hub Genes and Their Association with Immune Infiltration in Chronic Obstructive Pulmonary Disease by Bioinformatics Analysis

Yang¹,

Zhang²,

Liu³

et al. 2022

COPD

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Ferroptosis-Related Genes in Lung Adenocarcinoma: Prognostic Signature and Immune, Drug Resistance, Mutation Analysis

Abstract: Graphical AbstractFerroptosis genes in lung adenocarcinoma.

Cited by 59 publications

References 101 publications

LPIN1 Is a Regulatory Factor Associated With Immune Response and Inflammation in Sepsis

LPIN1 Is a Regulatory Factor Associated With Immune Response and Inflammation in Sepsis

Eucommia ulmoides Oliver-Tribulus terrestris L. Drug Pair Regulates Ferroptosis by Mediating the Neurovascular-Related Ligand-Receptor Interaction Pathway- A Potential Drug Pair for Treatment Hypertension and Prevention Ischemic Stroke

Identification of Ferroptosis-Related Hub Genes and Their Association with Immune Infiltration in Chronic Obstructive Pulmonary Disease by Bioinformatics Analysis

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