Comprehensive analysis pinpoints CCNA2 as a prognostic and immunological biomarker in non-small cell lung cancer.

Abstract

Background: Lung cancer is a leading cause of morbidity and mortality globally. Despite advances in targeted and immunotherapies, overall survival (OS) rates remain suboptimal. Cyclin-A2 (CCNA2), known for its upregulation in various tumors and role in tumorigenesis, has an undefined function in non-small cell lung cancer (NSCLC).

Methods: We analyzed three microarray datasets from the Gene Expression Omnibus (GEO) repository to identify differentially expressed genes. Using STRING, we constructed a protein-protein interaction (PPI) network to pinpoint hub genes. The expression and prognostic relevance of CCNA2 were validated using GEPIA and the Kaplan-Meier plotter. Clinicopathological correlations were assessed via the Human Protein Atlas (HPA) and UALCAN databases. qRT-PCR and immunohistochemistry (IHC) were performed to validate CCNA2 mRNA and protein levels. Loss-of-function assays in lung cancer cell lines evaluated the biological role of CCNA2. Immune infiltration and single-cell sequencing were also explored.

Results: Analysis of GSE18842, GSE101929, and GSE116959 datasets identified 321 upregulated and 623 downregulated genes in NSCLC. CCNA2 was confirmed to be highly expressed in NSCLC through qRT-PCR and IHC, with overexpression correlating with advanced pathological stages and lymph node metastasis. The area under the curve (AUC) of CCNA2 indicating high diagnostic accuracy. Immune infiltration and single-cell sequencing revealed that CCNA2 expression was significantly associated with immune cell infiltration, particularly in Tprolif cells.

Conclusion: CCNA2 is upregulated in NSCLC and shows significant correlation with clinicopathological characteristics. Our findings suggest that CCNA2 may serve as a promising biomarker for both the prognosis and diagnosis of NSCLC.