Abstract
BACKGROUND: This study aims to investigate potential biomarkers associated with NSCLC-BM and elucidate their regulatory roles in critical pathways involved in cerebral metastatic dissemination. METHODS: The identified DEGs were subjected to functional enrichment analysis. PPI networks were predicted using the STRING database and visualized with Cytoscape. Hub genes were subsequently screened from the PPI network to construct a transcription TF-miRNA regulatory network. Subsequent analyses included: survival analysis, immune infiltration assessment and comprehensive mutational profiling. RESULTS: Among the 56 identified DEGs, 19 were upregulated while 37 were downregulated. GOntology enrichment analysis revealed significant enrichment in immune response, signaling receptor binding, and extracellular region. KEGG pathway analysis demonstrated predominant involvement in cytokine-cytokine receptor interaction and chemokine signaling pathway. Through Cytoscape-based screening, we identified 10 hub genes: CD19, CD27, IL7R, SELL, CCL5, CCR5, PRF1, GZMK, GZMA, and TIGIT. The TF-miRNA regulatory network analysis uncovered 6 transcription factors (STAT5A/B, NFKB1, EGR1, RELA, and CTCF) and 4 miRNAs(hsa-miR-204, hsa-miR-148b, hsa-miR-618, and hsa-miR-103) as critical transcriptional and post-transcriptional regulators of DEGs.Integrated analyses including Kaplan-Meier survival curves, immune infiltration profiling, and comprehensive mutational analysis demonstrated significant associations with brain metastatic progression in the studied cohort. CONCLUSION: This study provides novel biomarkers from a unique perspective for the diagnosis, prognosis, and development of molecular-targeted therapies or immunotherapies for brain metastasis in NSCLC.