Multi-Omics Analyses Identify ANLN as a Prognostic Biomarker for Recurrence and Metastasis in Non-Small Cell Lung Cancer.

BACKGROUND

Lung cancer recurrence and metastasis are major causes of cancer-related mortality, but the molecular determinants underlying these processes remain incompletely understood. This study aimed to identify key regulators of lung cancer progression through integrative analyses of bulk and single-cell transcriptomic datasets.

METHODS

Bulk transcriptomic and single-cell RNA sequencing data from multiple cohorts were integrated to identify genes associated with survival, recurrence, and metastasis. Tumor microenvironment features were further analyzed to prioritize core progression-related genes. ANLN was subsequently evaluated in independent single-cell datasets, followed by functional validation using CRISPR-Cas9-mediated gene knockout in lung cancer cells. Network-based drug prediction and molecular docking were performed to identify candidate compounds targeting ANLN-related programs.

RESULTS

ANLN was identified as a core progression-related gene associated with poor prognosis. ANLN was upregulated in recurrent and metastatic lung tumors and correlated with worse overall survival. Single-cell analyses showed that ANLN was predominantly expressed in epithelial and proliferating tumor cells and was associated with microenvironment remodeling, enhanced proliferative and migratory programs, and progression toward an invasive phenotype. These findings were validated in an independent single-cell dataset capturing the transition from in situ to invasive lung cancer. Functional experiments showed that ANLN deletion reduced proliferation and promoted apoptosis in lung cancer cells. Drug prediction and molecular docking identified several candidate compounds, among which Trifluridine and Monobenzone showed favorable binding potential and pro-apoptotic effects in lung cancer cells.

CONCLUSIONS

ANLN is a potential regulator of lung cancer recurrence and metastasis and marks a conserved invasion-prone epithelial state. ANLN-associated pathways may represent potential therapeutic targets in lung cancer.