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Aim: Prostate cancer (PCa) is the most common malignancy found in males worldwide. Although it is mostly indolent, PCa still poses a serious threat to long-term health. Materials & methods: The Cancer Genome Atlas data were randomly divided into training and validation groups. Least absolute shrinkage and selection operator regression on DNA methylation data in the training group was conducted to build the model, which was validated in the validation group. Weighted correlation network analysis was conducted on RNA-seq data to identify the therapy target. Functional validation (western blot, quantitative real-time PCR, cell transfection, Cell Counting Kit-8 assay, colony formation assay, wound healing assay and transwell invasion assay) for the target was conducted. Results: The model is an independent predictor of prognosis. The knockdown of FOXD1 inhibits cell proliferation, migration and invasion of PCa. Conclusion: The risk of patients could be evaluated by the model, which revealed that FOXD1 might promote poor prognosis.

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