Abstract:
Objective: To investigate the relationship between cyclin A2 (CCNA2) and prognosis in colon adenocarcinoma (COAD), and to explore the potential mechanisms underlying the impact of CCNA2 on COAD prognosis from the perspective of immune infiltration. Methods: Transcriptome data, clinicopathological information, and prognosis data of 496 patients with COAD were downloaded from The Cancer Genome Atlas (TCGA) database. Rstudio software was utilized to screen CCNA2 RNA-seq data, analyze its expression in COAD tissues, and conduct survival analysis. Correlation analysis between CCNA2 expression and clinicopathological features was performed based on the downloaded clinical data from TCGA. Additionally, 76 cases of colon cancer tissues, normal colon tissues, and corresponding clinicopathological information from Yueyang People's Hospital between August 2018 and August 2024 were collected. Immunohistochemistry (IHC) was used to detect CCNA2 expression, and the relationship between CCNA2 and clinicopathological features was analyzed using the χ2 test. Gene Set Enrichment Analysis (GSEA) was employed to explore the potential molecular functions of CCNA2 in COAD. Furthermore, the CIBERSORT algorithm, an immune infiltration analysis tool, was applied to calculate the correlation between CCNA2 and immune cell infiltration in COAD. Results: The TCGA database results indicated that CCNA2 expression was significantly higher in COAD tissues than in normal tissues (P<0.001). IHC results confirmed this finding, revealing higher CCNA2 expression in COAD tissues (P<0.001). Patients with high CCNA2 expression had significantly longer overall survival (OS), disease-free survival (DSS), and progression-free interval (PFI) compared to those with low expression (all P<0.05). CCNA2 expression was negatively correlated with clinicopathological features of COAD, including clinical grade, T stage, N stage, and M stage (all P<0.05). CCNA2 expression in normal colon tissues was significantly lower than that in all pathological grades of COAD tissues (all P<0.001). GSEA revealed enrichment of IL6-JAK-STAT3 signaling, Interferon α (IFN-α), and MYC-V2 targets in high CCNA2 expression, while apical junction complex (AJC), epithelial-to-mesenchymal transition (EMT), Hedgehog (Hh), Wnt/β-Catenin, and Kirsten rats sarcoma viral oncogene homolog (KRAS) pathways were enriched in low CCNA2 expression. CIBERSORT analysis showed that decreased CCNA2 expression was associated with regulatory T cells (Tregs) and macrophages M0, while increased CCNA2 expression correlated with six types of immune cells, including activated memory CD4 T cells, follicular helper T cells, and macrophages M1. Conclusion: CCNA2 is highly expressed in COAD and closely related to clinical grade and TNM staging, negatively impacting COAD prognosis. The loss of CCNA2 expression promotes COAD progression by increasing regulatory T cell infiltration, upregulating the KRAS pathway, enhancing Wnt/β-Catenin pathway expression, and reducing the number of macrophages M1, thereby influencing immune infiltration in COAD. Immune cell infiltration may be a potential mechanism underlying the impact of CCNA2 on COAD prognosis.
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