Prognostic Significance of CCDC8 in Bladder Cancer: Insights from Bioinformatics and Immunohistochemical Analysis

J Cancer. 2025 Jan 1;16(2):382-397. doi: 10.7150/jca.102655. eCollection 2025.

Abstract

Background: Pro-apoptotic coiled-coil domain containing 8 (CCDC8) has been linked to tumor progression and metastasis, yet its prognostic significance and underlying molecular mechanisms in bladder cancer remain to be elucidated. Materials and methods: This study utilized raw data from public databases along with a single-center retrospective case series. We performed bioinformatics analysis and immunohistochemistry to investigate the biological landscape of CCDC8 in various tumors, with a particular focus on bladder cancer. This involved examining its expression characteristics and prognostic value. Gene function enrichment analysis was conducted to perform functional annotation, evaluate the association between bladder cancer molecular subtypes and mutation spectra, and analyze the tumor immune microenvironment to predict treatment response sensitivity. Results: Our study identified CCDC8 as a novel prognostic marker for bladder cancer. We observed that high CCDC8 expression correlates with poor prognosis and a suboptimal response to immunotherapy in bladder cancer. CCDC8 was implicated in regulating tumor immune status, metabolic activity, and cell cycle-related signaling pathways, thereby influencing the biological behavior of tumor cells. Additionally, CCDC8 contributed to the suppression of the immune microenvironment, diminishing anti-tumor immune responses. Comprehensive characterization of CCDC8 was applied to prognostic prediction in bladder cancer, indicating that targeting CCDC8 may be a potential therapeutic strategy. Conclusions: These findings suggest that CCDC8 serves as an independent biomarker for predicting prognosis and immunotherapy efficacy for bladder cancer. Further investigation into its specific molecular mechanisms may offer new therapeutic strategies for treating bladder cancer.

Keywords: bladder cancer; computational biology and bioinformatics; pro-apoptotic coiled-coil domain containing 8 (CCDC8); tumor microenvironment.