Integrating Bioinformatics and Experimental Validation Identify CCNA2 as a Novel Prognostic Biomarker and Tumor Promoter via the PI3K/AKT Pathway in Lung Adenocarcinoma.

PURPOSE: To investigate the prognostic value of cell cyclin A2 (CCNA2) in lung adenocarcinoma (LUAD) and to explore its mechanisms in promoting cancer progression. PATIENTS AND METHODS: In this study, we employed an integrated strategy combining bioinformatics, clinical analysis and molecular biology to elucidate the role of CCNA2 in LUAD. First, comprehensive bioinformatics analyses were performed using public datasets. This included detecting the differential expression of CCNA2 in LUAD versus normal tissues, analyzing its correlation with patient survival and clinical characteristics, and employing Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) analysis to predict the functions of CCNA2-associated genes. The relationship between CCNA2 expression and immune infiltration was further examined via the tumor immune estimation resource (TIMER) platform. The expression level of CCNA2 was also confirmed through reverse transcription-quantitative PCR and Western blotting. Additionally, the biological function of CCNA2 was evaluated by constructing an in vitro transfection model. RESULTS: The results of the present study indicated that CCNA2 was upregulated in LUAD tissues. Cox regression analysis revealed that CCNA2 upregulation is a independent prognostic biomarker for LUAD. Additionally, CCNA2 was markedly associated with immune cell infiltration and immune checkpoint molecules. The results of in vitro experiments confirmed that knockdown of CCNA2 significantly inhibited the proliferation, invasion and migration of H1975 and H1299 cells. Furthermore, CCNA2 was found to promote the invasion and migration of lung cancer cells through the PI3K/AKT signaling pathway. CONCLUSION: The present research identified the prognostic signature and biological function of CCNA2 in LUAD, which suggested that CCNA2 may be a potential prognostic biomarker and a pivotal oncogenic driver for this disease.