|Table of Contents|

The impact of key genes related to iron death and oxidative stress on the immune microenvironment and survival prognosis in lung adenocarcinoma

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2025 03
Page:
409-416
Research Field:
Publishing date:

Info

Title:
The impact of key genes related to iron death and oxidative stress on the immune microenvironment and survival prognosis in lung adenocarcinoma
Author(s):
LI Yong1; SHI Danfei2; LI Xinmin3; JI Longfei2
1.School of Medical Technology and Information Engineering,Zhejiang Chinese Medical University,Zhejiang Hangzhou 310053,China；2.The First Affiliated Hospital of Huzhou University,Zhejiang Huzhou 313000,China；3.Chongqing Hospital of Traditional Chinese Medicine,Chongqing 400000,China.
Keywords:
lung adenocarcinoma (LUAD); iron death; oxidative stress; immune infiltration; single-cell sequencing
PACS:
R734.2
DOI:
10.3969/j.issn.1672-4992.2025.03.008
Abstract:
Objective:To identify differentially expressed key genes associated with iron death and oxidative stress in lung adenocarcinoma (LUAD) based on bioinformatics,and to explore their potential roles in immune infiltration and survival prognosis.Methods:By analyzing transcriptome data from Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) databases,differential expression analysis and cross identification with iron death and oxidative stress-related genes were used to identify key genes.Subsequently,bioinformatics methods were used to perform survival analysis and immune cell infiltration analysis on key genes,while evaluating drug interactions.Single cell RNA sequencing data were used to explore the expression characteristics of key genes in different cell types.Finally,qPCR experiments were conducted on the whole blood samples collected at the First People's Hospital of Huzhou.Results:This study identified two genes,DUOX1 and IL33,whose expression in LUAD tissue was significantly lower than that in normal tissue and significantly correlated with patient survival.Immunoassay showed a significant correlation between DUOX1 and IL33 and infiltration of multiple immune cells.Single cell analysis further revealed the expression patterns of these two genes in different immune cell subpopulations,enhancing our understanding of their roles in the tumor microenvironment.In addition,the drug interaction analysis results indicated that IL33 may become a potential therapeutic target for LUAD,and the qPCR experimental results were consistent with the validation results of the TCGA database.Conclusion:DUOX1 and IL33 may play important roles in LUAD,and their potential as biomarkers provides new directions for early diagnosis and targeted therapy of LUAD,laying the foundation for further research.

References:

［1］ LI D,SHI J,DONG X,et al.Epidemiological characteristics and risk factors of lung adenocarcinoma:A retrospective observational study from North China［J］.Frontiers in Oncology,2022,12:892571.
［2］ LI F,LI F,ZHAO D,et al.Predictors of cancer-specific survival and overall survival among patients aged≥60 years with lung adenocarcinoma using the SEER database［J］.Journal of International Medical Research,2024,52(4):03000605241240993.
［3］ 孟繁昊,王珑.基于氧化应激-铁死亡针刺抗抑郁中枢机制研究进展［J］.现代中西医结合杂志,2024,33(12):1740-1745,1752. MENG FH,WANG L.Based on the antidepressant central mechanism of oxidative stress-iron death acupuncture ［J］.Journal of Modern Integrated Traditional Chinese and Western Medicine,2024,33 (12):1740-1745,1752.
［4］ ZHANG L,LUO YL,XIANG Y,et al.Ferroptosis inhibitors:past,present and future［J］.Frontiers in Pharmacology,2024,15:1407335.
［5］ BAI R,GUO J,YE XY,et al.Oxidative stress:The core pathogenesis and mechanism of Alzheimer's disease［J］.Ageing Research Reviews,2022,77:1568-1637.
［6］ ZHENG Q,MIN S,ZHOU Q.Identification of potential diagnostic and prognostic biomarkers for LUAD based on TCGA and GEO databases［J］.Bioscience Reports,2021,41(6):BSR20204370.
［7］ GAO P,ZOU K,XIAO L,et al.High expression of PTGES3 is an independent predictive poor prognostic biomarker and correlates with immune infiltrates in lung adenocarcinoma［J］.International Immunopharmacology,2022,110:108954.
［8］ LI Y,CAI Y,JI L,et al.Machine learning and bioinformatics analysis of diagnostic biomarkers associated with the occurrence and development of lung adenocarcinoma［J］.PeerJ,2024,12:e17746.
［9］ ZHOU S,LU H,XIONG M.Identifying immune cell infiltration and effective diagnostic biomarkers in rheumatoid arthritis by bioinformatics analysis［J］.Frontiers in Immunology,2021,12:726747.
［10］ NIU R,ZHAO F,DONG Z,et al.A stratification system of ferroptosis and iron-metabolism related LncRNAs guides the prediction of the survival of patients with esophageal squamous cell carcinoma［J］.Frontiers in Oncology,2022,12:1010074.
［11］ WU Z,WANG L,WEN Z,et al.Integrated analysis identifies oxidative stress genes associated with progression and prognosis in gastric cancer［J］.Scientific Reports,2021,11(1):3292.
［12］ LEI Y,TANG R,XU J,et al.Construction of a novel risk model based on the random forest algorithm to distinguish pancreatic cancers with different prognoses and immune microenvironment features［J］.Bioengineered,2021,12(1):3593-3602.
［13］ DIGRE A,LINDSKOG C.The human protein atlas-spatial localization of the human proteome in health and disease［J］.Protein Science,2021,30(1):218-233.
［14］ FAN C,CHEN F,CHEN Y,et al.irGSEA:the integration of single-cell rank-based gene set enrichment analysis［J］.Briefings in Bioinformatics,2024,25(4):bbae243.
［15］ CANNON M,STEVENSON J,STAHL K,et al.DGIdb 5.0:rebuilding the drug-gene interaction database for precision medicine and drug discovery platforms［J］.Nucleic Acids Research,2024,52(D1):D1227-D1235.
［16］ DONCHEVA NT,MORRIS JH,HOLZE H,et al.Cytoscape stringApp 2.0:analysis and visualization of heterogeneous biological networks［J］.Journal of Proteome Research,2022,22(2):637-646.
［17］LI MJ,YAN SB,CHEN G,et al.Upregulation of CCNB2 and its perspective mechanisms in cerebral ischemic stroke and all subtypes of lung cancer:a comprehensive study［J］.Frontiers in Integrative Neuroscience,2022,16:854540.
［18］ ZHANG P,YANG Z,LIU Z,et al.Deciphering lung adenocarcinoma evolution:Integrative single-cell genomics identifies the prognostic lung progression associated signature［J］.Journal of Cellular and Molecular Medicine,2024,28(11):e18408.
［19］ ASHTIWI NM,SARR D,RADA B.DUOX1 in mammalian disease pathophysiology［J］.Journal of Molecular Medicine,2021,99(6):743-754.
［20］ GANESH JM,PRERANA P,DHARMARAJAN A,et al.Modulation of reactive oxygen species in cancers:recent advances［J］.Free Radical Research,2022,56(5-6):447-470.
［21］ WANG SL,WU Y,KONATE M,et al.Exogenous DNA enhances DUOX2 expression and function in human pancreatic cancer cells by activating the cGAS-STING signaling pathway［J］.Free Radical Biology and Medicine,2023,205:262-274.
［22］ WEI C,LI L,QIAO Y,et al.Ferroptosis-related genes DUOX1 and HSD17B11 affect tumor microenvironment and predict overall survival of lung adenocarcinoma patients［J］.Medicine,2024,103(22):e38322.
［23］ 韩鸿举,苏子阳,王玺,等.白细胞介素33在肿瘤免疫中的作用及信号通路研究进展［J］.生理科学进展,2022,53(2):152-155. HAN HJ,SU ZY,WANG X,et al.The role and signaling pathway of interleukin 33 in tumor immunity ［J］.Progress in Physiological Science,2022,53(2):152-155.
［24］ 刘茜茜,陆地,胡嘉华,等.白细胞介素-33在肿瘤中的双重作用［J］.中南大学学报(医学版),2021,46(02):169-175. LIU QQ,LU D,HU JH,et al.Dual role of interleukin-33 in tumors ［J］.Journal of Central South University (Medical Edition),2021,46(02):169-175.
［25］ YUE J,GUO H,XU P,et al.Combination of IL-33 with PD-1 blockade augment mILC2s-mediated anti-tumor immunity［J］.Cancer Immunology,Immunotherapy,2024,73(4):65.
［26］ LI J,SHEN D,TANG J,et al.IL33 attenuates ventricular remodeling after myocardial infarction through inducing alternatively activated macrophages ethical standards statement［J］.European Journal of Pharmacology,2019,854:307-319.

Memo

Memo:
National Natural Science Foundation of China(No.82202649）；国家自然科学基金（编号：82202649）；浙江省医药卫生科技计划项目（编号：2023KY318）
Last Update: 1900-01-01