CCNA2 Expression and Its Prognostic Significance in cholangiocarcinoma

Background: Cholangiocarcinoma（CCA）is a rare malignancy and it has become a significant health burden worldwide. An increasing number of studies have demonstrated the crucial correlation of immunophenotypic characteristics modifications in resected specimen of CCA. However, the accurate prognostic markers is still lacking in the prognosis of CCA. Methods: : Gene expression profiles and clinical data of CCA were downloaded from the Gene Expression Omnibus（GEO）database. GO and KEGG analysis were applied for differentially expressed genes in cholangiocarcinoma, and PPI network was constructed in Cytoscape software. The expression difference of Cyclin A2 (CCNA2) in CCA tissues and adjacent noncancerous tissues was analyzed by R software and verified by comprehensive analysis. The relationship between CCNA2 expression and immune infiltration was assessed in the the Cancer Genome Atlas (TCGA) database. Kaplan–Meier survival analysis were chosen to assess the effect of CCNA2 expression on survival. Gene set enrichment analysis (GSEA) was used to screen the signaling pathways involved in CCA between the low and the high CCNA2 expression group. Results: : The expression of CCNA2 in CCA was significantly higher than that in adjacent cancerous tissues ( P < 0.001) from the GEO database. The top 10 hub genes were mined by the Degree, MCC, and Closeness method​ based on the PPI network. CCNA2 was screened as the candidates to be further analyzed and validated. The Kaplan–Meier curves suggested that patients with high CCNA2 expression had a poor prognosis. Multivariate analysis showed that a high expression of CCNA2 was an important independent predictor of poor overall survival ( P = 0.033). Cibersort analysis showed that the fraction of T cells CD4 (naive, P < 0.0001), T cells CD4 (memory, P = 0.0055), T cells (follicular, P = 0.0063), NK cells ( P = 0.0149), dendritic cells ( P = 0.029), neutrophils ( P = 0.0113) is significantly correlated with the expression of CCNA2, which highlighted the CCNA2 expression in immune infiltrates. GSEA indicated that 12 signaling pathways were evidently enriched in samples with the high-CCNA2 phenotype. Conclusions: : CCNA2 might act as an oncogene in the progression of CCA and could be regarded as a potential prognostic indicator and therapeutic target for CCA.