Integrated bioinformatics analysis of key genes and pathways in lung adenocarcinoma occurrence, development, and survival
Introduction: Lung adenocarcinoma (LUAD) remains a major cause of cancer mortality, and robust molecular markers are still needed to improve risk stratification.
Objective: This study aimed to identify reproducible genes and pathways associated with LUAD development and patient outcome through an integrated analysis of public transcriptomic datasets.
Methods: Four Gene Expression Omnibus (GEO) datasets (GSE10072, GSE18842, GSE19804, and GSE33532) were used as discovery cohorts to identify common tumor-versus-non-tumor differentially expressed genes (DEGs), followed by LUAD-specific external evaluation. Common DEGs were integrated by protein–protein interaction analysis and functional enrichment. Candidate hub genes were subsequently evaluated for expression, pathological stage, overall survival, promoter methylation, immune-cell infiltration, and smoking-related expression using Gene Expression Profiling Interactive Analysis, University of Alabama at Birmingham Cancer Data Analysis Portal, and Tumor Immune Estimation Resource.
Results: We identified 151 common DEGs, including 33 upregulated and 118 downregulated genes. Enrichment analysis highlighted extracellular matrix-related functions and the phosphoinositide 3-kinase–protein kinase B signaling pathway. Eight hub genes were associated with overall survival. Among them, ZWINT, TOP2A, RRM2, NEK2, and AGER showed additional associations with promoter methylation and/or immune infiltration. Smoking-related expression differences were observed for ZWINT, TOP2A, RRM2, and NEK2, whereas AGER showed no significant association with smoking status.
Conclusion: Integrating four independent GEO datasets with complementary validation analyses identified ZWINT, TOP2A, RRM2, NEK2, and AGER as reproducible LUAD-associated candidates. These findings support further experimental and clinical validation of these genes as potential components of biomarker panels rather than as established therapeutic targets.
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