Department of Sports Medicine, Huazhong University of Science and Technology Union Shenzhen Hospital, The 6th Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, China.
Department of Urology, Huazhong University of Science and Technology Union Shenzhen Hospital, The 6th Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, China.
Aging (Albany NY). 2023 Jul 25;15(14):7161-7186. doi: 10.18632/aging.204900.
Immunotherapy has become a revolutionary treatment for cancer and brought new vitality to tumor immunity. Bone metastases are the most prevalent metastatic site for advanced prostate cancer (PCa). Therefore, finding new immunotherapy targets in PCa patients with bone metastasis is urgently needed. We conducted an elaborative bioinformatics study of immune-related genes (IRGs) and tumor-infiltrating immune cells (TIICs) in PCa bone metastases. Databases were integrated to obtain RNA-sequencing data and clinical prognostic information. Univariate and multivariate Cox regression analyses were conducted to construct an overall survival (OS) prediction model. GSE32269 was analyzed to acquire differentially expressed IRGs. The OS prediction model was established by employing six IRGs (MAVS, HSP90AA1, FCGR3A, CTSB, FCER1G, and CD4). The CIBERSORT algorithm was adopted to assess the proportion of TIICs in each group. Furthermore, Transwell, MTT, and wound healing assays were employed to determine the effect of MAVS on PCa cells. High-risk patients had worse OS compared to the low-risk patients in the training and validation cohorts. Meanwhile, clinically practical nomograms were generated using these identified IRGs to predict the 3- and 5-year survival rates of patients. The infiltration percentages of some TIICs were closely linked to the risk score of the OS prediction model. Some tumor-infiltrating immune cells were related to the OS. FCGR3A was closely correlated with some TIICs. experiments verified that up-regulation of MAVS suppressed the proliferation and metastatic abilities of PCa cells. Our work presented a thorough interpretation of TIICs and IRGs for illustrating and discovering new potential immune checkpoints in bone metastases of PCa.
免疫疗法已成为癌症的一种革命性治疗方法，为肿瘤免疫带来了新的活力。骨转移是晚期前列腺癌（PCa）最常见的转移部位。因此，迫切需要在患有骨转移的 PCa 患者中找到新的免疫治疗靶点。我们对 PCa 骨转移中的免疫相关基因（IRGs）和肿瘤浸润免疫细胞（TIICs）进行了详细的生物信息学研究。整合数据库以获取 RNA-seq 数据和临床预后信息。进行单变量和多变量 Cox 回归分析以构建总生存期（OS）预测模型。分析 GSE32269 以获得差异表达的 IRGs。通过使用六个 IRGs（MAVS、HSP90AA1、FCGR3A、CTSB、FCER1G 和 CD4）来建立 OS 预测模型。采用 CIBERSORT 算法评估每组 TIICs 的比例。此外，通过 Transwell、MTT 和划痕愈合实验来确定 MAVS 对 PCa 细胞的影响。在训练和验证队列中，高危患者的 OS 明显差于低危患者。同时，使用这些鉴定的 IRGs 生成了临床实用的列线图，以预测患者的 3 年和 5 年生存率。一些 TIICs 的浸润百分比与 OS 预测模型的风险评分密切相关。一些肿瘤浸润免疫细胞与 OS 相关。FCGR3A 与一些 TIICs密切相关。实验验证了上调 MAVS 抑制了 PCa 细胞的增殖和转移能力。我们的工作全面解析了 TIICs 和 IRGs，为阐明和发现 PCa 骨转移中的新潜在免疫检查点提供了依据。
