Exploration of shared biomarkers and mechanisms in systemic lupus erythematous and lung cancer via bioinformatics analysis

Systemic lupus erythematosus (SLE) patients exhibit a heightened risk of developing lung cancer, yet the underlying molecular mechanisms remain poorly understood. This study aimed to identify shared genetic factors linking SLE and LC using publicly available transcriptomic data from the Gene Express...

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Main Authors: Chueh-Hsuan Hsu, Shuo-Chueh Chen, Yung-Luen Yu
Format: Article
Language:English
Published: Elsevier 2025-12-01
Series:Journal of Translational Autoimmunity
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Online Access:http://www.sciencedirect.com/science/article/pii/S2589909025000395
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author Chueh-Hsuan Hsu
Shuo-Chueh Chen
Yung-Luen Yu
author_facet Chueh-Hsuan Hsu
Shuo-Chueh Chen
Yung-Luen Yu
author_sort Chueh-Hsuan Hsu
collection DOAJ
description Systemic lupus erythematosus (SLE) patients exhibit a heightened risk of developing lung cancer, yet the underlying molecular mechanisms remain poorly understood. This study aimed to identify shared genetic factors linking SLE and LC using publicly available transcriptomic data from the Gene Expression Omnibus (GEO). Through integrated differentially expressed gene (DEG) analysis and weighted gene co-expression network analysis (WGCNA), we identified five genes consistently upregulated in both SLE and lung cancer. Gene set enrichment analysis (GSEA) revealed that these shared genes were enriched in inflammatory pathways, particularly those involving interferon-alpha, interferon-gamma, and general inflammatory responses. We applied least absolute shrinkage and selection operator (LASSO) regression to pinpoint potential diagnostic biomarkers and identified two key candidates: AIM2 and SLC26A8. These biomarkers demonstrated robust diagnostic performance with area under the ROC curve (AUC) values exceeding 0.75 in both training and validation cohorts. Immune infiltration and survival analyses using The Cancer Genome Atlas (TCGA) further supported their clinical relevance. Notably, high AIM2 expression was significantly associated with poorer overall survival in female lung adenocarcinoma patients (P = 0.03), and SLC26A8 expression was significantly linked to survival outcomes only in patients with a history of smoking (P = 0.01). These findings are particularly meaningful in SLE, where most patients are female and smoking is a known risk factor. Our study enhances the understanding of autoimmune-driven carcinogenesis and opens new avenues for precision medicine strategies in managing patients with SLE at risk for lung cancer.
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spelling doaj-art-e0d4e5e8a7034906bf05a855a67be81b2025-08-20T03:59:22ZengElsevierJournal of Translational Autoimmunity2589-90902025-12-011110030410.1016/j.jtauto.2025.100304Exploration of shared biomarkers and mechanisms in systemic lupus erythematous and lung cancer via bioinformatics analysisChueh-Hsuan Hsu0Shuo-Chueh Chen1Yung-Luen Yu2Graduate Institute of Biomedical Sciences, College of Medicine, China Medical University, Taichung, 406040, TaiwanSchool of Medicine, China Medical University, Taichung, 406040, Taiwan; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, 404327, TaiwanGraduate Institute of Biomedical Sciences, College of Medicine, China Medical University, Taichung, 406040, Taiwan; Institute of Translational Medicine and New Drug Development, China Medical University, Taichung, 406040, Taiwan; Center for Molecular Medicine, China Medical University Hospital, Taichung, 404327, Taiwan; Department of Medical Laboratory Science and Biotechnology, Asia University, Taichung, 413305, Taiwan; Corresponding author. Graduate Institute of Biomedical Sciences, College of Medicine, China Medical University, Taichung, 406040, Taiwan.Systemic lupus erythematosus (SLE) patients exhibit a heightened risk of developing lung cancer, yet the underlying molecular mechanisms remain poorly understood. This study aimed to identify shared genetic factors linking SLE and LC using publicly available transcriptomic data from the Gene Expression Omnibus (GEO). Through integrated differentially expressed gene (DEG) analysis and weighted gene co-expression network analysis (WGCNA), we identified five genes consistently upregulated in both SLE and lung cancer. Gene set enrichment analysis (GSEA) revealed that these shared genes were enriched in inflammatory pathways, particularly those involving interferon-alpha, interferon-gamma, and general inflammatory responses. We applied least absolute shrinkage and selection operator (LASSO) regression to pinpoint potential diagnostic biomarkers and identified two key candidates: AIM2 and SLC26A8. These biomarkers demonstrated robust diagnostic performance with area under the ROC curve (AUC) values exceeding 0.75 in both training and validation cohorts. Immune infiltration and survival analyses using The Cancer Genome Atlas (TCGA) further supported their clinical relevance. Notably, high AIM2 expression was significantly associated with poorer overall survival in female lung adenocarcinoma patients (P = 0.03), and SLC26A8 expression was significantly linked to survival outcomes only in patients with a history of smoking (P = 0.01). These findings are particularly meaningful in SLE, where most patients are female and smoking is a known risk factor. Our study enhances the understanding of autoimmune-driven carcinogenesis and opens new avenues for precision medicine strategies in managing patients with SLE at risk for lung cancer.http://www.sciencedirect.com/science/article/pii/S2589909025000395Systemic lupus erythematosusLung cancerTumorigenesisTumor immune microenvironmentAIM2SLC26A8
spellingShingle Chueh-Hsuan Hsu
Shuo-Chueh Chen
Yung-Luen Yu
Exploration of shared biomarkers and mechanisms in systemic lupus erythematous and lung cancer via bioinformatics analysis
Journal of Translational Autoimmunity
Systemic lupus erythematosus
Lung cancer
Tumorigenesis
Tumor immune microenvironment
AIM2
SLC26A8
title Exploration of shared biomarkers and mechanisms in systemic lupus erythematous and lung cancer via bioinformatics analysis
title_full Exploration of shared biomarkers and mechanisms in systemic lupus erythematous and lung cancer via bioinformatics analysis
title_fullStr Exploration of shared biomarkers and mechanisms in systemic lupus erythematous and lung cancer via bioinformatics analysis
title_full_unstemmed Exploration of shared biomarkers and mechanisms in systemic lupus erythematous and lung cancer via bioinformatics analysis
title_short Exploration of shared biomarkers and mechanisms in systemic lupus erythematous and lung cancer via bioinformatics analysis
title_sort exploration of shared biomarkers and mechanisms in systemic lupus erythematous and lung cancer via bioinformatics analysis
topic Systemic lupus erythematosus
Lung cancer
Tumorigenesis
Tumor immune microenvironment
AIM2
SLC26A8
url http://www.sciencedirect.com/science/article/pii/S2589909025000395
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AT shuochuehchen explorationofsharedbiomarkersandmechanismsinsystemiclupuserythematousandlungcancerviabioinformaticsanalysis
AT yungluenyu explorationofsharedbiomarkersandmechanismsinsystemiclupuserythematousandlungcancerviabioinformaticsanalysis