Prognostic role of CDCA3 in lung adenocarcinoma with immune infiltration

Lung cancer is a leading cause of cancer-related deaths, often resistant to conventional therapies like platinum-based chemotherapy. Identifying new biomarkers and therapeutic targets is essential for improving outcomes. In this study, we explored the role of CDCA3 in lung adenocarcinoma (LUAD) as a prognostic marker and its association with immune cell infiltration and immunotherapy. Using data from The Cancer Genome Atlas (TCGA), we evaluated CDCA3 expression and its prognostic significance through Kaplan-Meier survival analysis. Our results showed that CDCA3 was significantly upregulated in LUAD tumor tissues compared to normal tissues, with higher CDCA3 expression linked to poorer overall survival. Additionally, CDCA3 expression correlated with clinical features such as age, gender, cancer stage, and smoking status. Immune infiltration analysis revealed significant associations with CD4-activated memory T cells and macrophages. Single‑cell transcriptomics revealed that the proportions of CD8⁺ exhausted T cells, CD8⁺ cytotoxic T cells, M1 macrophages and M2 macrophages varied in association with CDCA3 expression levels in LUAD. CDCA3 expression also correlated with immune scores and immune checkpoint gene expression. Drug sensitivity analysis using the "oncoPredict" R package suggested that CDCA3 expression may influence chemotherapy responses. In vitro experiments in A549 cells showed that CDCA3 knockdown significantly reduced CDCA3 expression at both the mRNA and protein levels. While flow cytometry indicated increased apoptosis in CDCA3-knockdown cells, suggesting CDCA3's role in promoting LUAD cell proliferation and survival. These findings indicated that CDCA3 could serve as a valuable prognostic biomarker in LUAD, influencing prognosis, immune response, and drug sensitivity, potentially guiding therapeutic and immunotherapy decisions.