Pan-cancer analysis identifies CDCA3 as a novel prognostic marker associated with immune infiltration in lung adenocarcinoma through bioinformatics analysis

BACKGROUND: Lung adenocarcinoma (LUAD) is the most common subtype of lung malignancy. However, the expression of cell division cycle-associated protein-3 (CDCA3) and its significance in LUAD remain unclear. In this study, we investigated the functional role of CDCA3 in LUAD through bioinformatics analysis and expected to provide a new direction for clinical treatment. METHODS: The expression of CDCA3 was analyzed by online database. The association between the expression of CDCA3 and clinical parameters with LUAD was explored in TCGA. Survival and independent prognostic analysis were performed by TCGA database and the GSE30219 and GSE31210 datasets. Furthermore, Enrichment analyses were conducted to analyze the functions of CDCA3. Afterward, the relationship between CDCA3 and immune infiltration was investigated. Additionally, a competing endogenous RNA (ceRNA) regulatory network related to CDCA3 was constructed. Finally, CDCA3 expression was validated in clinical tissues by immunohistochemistry (IHC), real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), and western blotting (WB). RESULTS: CDCA3 expression was upregulated in 20 tumors and was significantly higher in LUAD compared with normal tissues in3 datasets. In addition, CDCA3 was significantly correlated with age, gender, stage, N, and smoking status. Kaplan-Meier survival curves showed that LUAD samples with higher CDCA3 expression were associated with poorer overall survival (OS) and disease-free survival (DFS). Univariate Cox regression analysis showed that the p value of CDCA3 expression was less than 0.05 (P<0.05) and it appeared in the results of multivariate Cox regression analysis (HR ≥1), indicating that CDCA3 can be used as an independent prognostic factor for LUAD. Intriguingly, Gene Set Enrichment Analysis (GSEA) suggested that CDCA3 was correlated with DNA-related terms and metabolic-related pathways in LUAD. CDCA3 expression was correlated with four immune scores and 14 immune cells in different groups. Next, a ceRNA network was constructed with CDCA3, and the experimental results of IHC, qRT-PCR, and WB were consistent with the bioinformatic analysis. CONCLUSIONS: CDCA3 could serve as a prognostic biomarker for LUAD.