This study investigates the role of monocyte-associated features in the prognosis and immunotherapy of prostate cancer (PRAD). Using the TCGA-PRAD dataset and various bioinformatics methods, including WGCNA, machine learning, and functional analysis, the researchers identified 14 monocyte-related genes associated with PRAD prognosis. A diagnostic model was developed using multiple machine learning algorithms, while a prognostic model was constructed using the LASSO algorithm. The gene CCNA2 was identified as the most significant gene related to monocyte prognosis in PRAD. Functional analysis revealed that CCNA2 is involved in cell cycle regulation, cellular senescence, and immune responses. Additionally, molecular docking analysis showed that CCNA2 has a strong binding affinity with drugs targeting PRAD. Experimental validation confirmed the expression and prognostic value of CCNA2 in PRAD. The study also found that high levels of HLA-DR expressing monocytes may promote PRAD progression. These findings suggest that monocyte-related genes, particularly CCNA2, could serve as potential biomarkers and therapeutic targets for PRAD. The study highlights the importance of monocyte heterogeneity in PRAD and provides new insights into the mechanisms underlying tumor immune infiltration and immunotherapy.This study investigates the role of monocyte-associated features in the prognosis and immunotherapy of prostate cancer (PRAD). Using the TCGA-PRAD dataset and various bioinformatics methods, including WGCNA, machine learning, and functional analysis, the researchers identified 14 monocyte-related genes associated with PRAD prognosis. A diagnostic model was developed using multiple machine learning algorithms, while a prognostic model was constructed using the LASSO algorithm. The gene CCNA2 was identified as the most significant gene related to monocyte prognosis in PRAD. Functional analysis revealed that CCNA2 is involved in cell cycle regulation, cellular senescence, and immune responses. Additionally, molecular docking analysis showed that CCNA2 has a strong binding affinity with drugs targeting PRAD. Experimental validation confirmed the expression and prognostic value of CCNA2 in PRAD. The study also found that high levels of HLA-DR expressing monocytes may promote PRAD progression. These findings suggest that monocyte-related genes, particularly CCNA2, could serve as potential biomarkers and therapeutic targets for PRAD. The study highlights the importance of monocyte heterogeneity in PRAD and provides new insights into the mechanisms underlying tumor immune infiltration and immunotherapy.