Zhao Xiaojie, Yu Xin, Li Wenge, Wang Lei, Weng Xiaodong, Liu Cheng, Liu Xiuheng
Department of Urology, Renmin Hospital of Wuhan University, 430060 Wuhan, Hubei, China.
Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, 430060 Wuhan, Hubei, China.
J Cancer. 2025 Jan 1;16(2):382-397. doi: 10.7150/jca.102655. eCollection 2025.
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. 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. 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. 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.
促凋亡卷曲螺旋结构域蛋白8（CCDC8）与肿瘤进展和转移有关，但其在膀胱癌中的预后意义和潜在分子机制仍有待阐明。本研究利用公共数据库的原始数据以及单中心回顾性病例系列。我们进行了生物信息学分析和免疫组织化学，以研究CCDC8在各种肿瘤中的生物学情况，尤其关注膀胱癌。这包括检查其表达特征和预后价值。进行基因功能富集分析以进行功能注释，评估膀胱癌分子亚型与突变谱之间的关联，并分析肿瘤免疫微环境以预测治疗反应敏感性。我们的研究确定CCDC8为膀胱癌的一种新的预后标志物。我们观察到CCDC8高表达与膀胱癌预后不良和免疫治疗反应欠佳相关。CCDC8参与调节肿瘤免疫状态、代谢活性和细胞周期相关信号通路，从而影响肿瘤细胞的生物学行为。此外，CCDC8导致免疫微环境受到抑制，削弱抗肿瘤免疫反应。对CCDC8的全面表征应用于膀胱癌的预后预测，表明靶向CCDC8可能是一种潜在的治疗策略。这些发现表明，CCDC8可作为预测膀胱癌预后和免疫治疗疗效的独立生物标志物。对其具体分子机制的进一步研究可能为治疗膀胱癌提供新的治疗策略。
