CCDC78 is required for prostate cancer cell growth and serves as a prognostic biomarker for high-risk disease

As the second most common malignancy among men worldwide, prostate cancer is commonly diagnosed through PSA testing and puncture biopsy. However, these methods have limitations in risk assessment. Clinically, low-risk patients typically require only active monitoring rather than immediate intervention, whereas high-risk patients need timely treatment. Therefore, more precise biomarkers are needed to identify prostate cancer at different risk levels.

Differentially expressed genes (DEGs) between high-risk and low-risk prostate cancer samples were identified using RNA-seq. Systematic bioinformatics approaches, including WGCNA, LASSO, and Cox regression analyses, were performed to identify potential prognostic biomarkers. Time-dependent receiver operating characteristic (ROC) curves were used to evaluate the accuracy of the identified biomarkers. Additionally, GO and KEGG enrichment analyses were conducted on genes coexpressed with the prognostic biomarker. A series of siRNA-mediated knockdown experiments, including proliferation, apoptosis, colony formation, and spheroid formation assays, were performed to assess the functional roles of the prognostic biomarker in prostate cancer.

RNA-seq revealed that 656 genes were upregulated and 426 genes were downregulated in high-risk prostate cancer. Using systematic bioinformatics approaches, we identified CCDC78 as a potential prognostic biomarker for high-risk prostate cancer. Time-dependent ROC curve analysis showed that the AUCs of CCDC78 were all greater than 0.7 at the 1-, 3-, and 5-year time points. GO enrichment analysis revealed that genes coexpressed with CCDC78 were mainly enriched in tumor immune-related signaling pathways. Furthermore, siRNA-mediated knockdown of CCDC78 significantly inhibited proliferation, colony formation, and spheroid formation, while inducing apoptosis in prostate cancer cells. Importantly, knockdown of CCDC78 reduced expression of the prostate cancer driver factor AR, and partially restored proliferative activity in AR-overexpressing LNCaP cells compared with wild-type cells.

Our study is the first to reveal that CCDC78 is required for the growth of prostate cancer cells and serves as a prognostic biomarker for high-risk disease.