Department of Physiology, School of Basic Medical Science, Chongqing Medical University, Chongqing 400016, China.
Department of Biostatistics, School of Public Health, Chongqing Medical University, Chongqing 400016, China.
Int J Mol Sci. 2024 Aug 26;25(17):9235. doi: 10.3390/ijms25179235.
Dendritic cells (DCs) serve as key regulators in tumor immunity, with activated DCs potentiating antitumor responses through the secretion of pro-inflammatory cytokines and the expression of co-stimulatory molecules. Most current studies focus on the relationship between DC subgroups and clear-cell renal-cell carcinoma (ccRCC), but there is limited research on the connection between DCs and ccRCC from the perspective of immune activation. In this study, activated DC genes were identified in both bulk and single-cell RNA-seq data. A prognostic model related to activated DCs was constructed using univariate, multivariate Cox regression and LASSO regression. The prognostic model was validated in three external validation sets: GSE167573, ICGC, and E-MTAB-1980. The prognostic model consists of five genes, , , , , and . The expression of these genes was validated in tissue samples using qRT-PCR. Stratified analysis revealed that the prognostic model was able to better predict outcomes in advanced ccRCC patients. The risk scores were associated with tumor progression, tumor mutation burden, immune cell infiltration, and adverse outcomes of immunotherapy. Notably, there was a strong correlation between the expression of the five genes and the sensitivity to JQ1, a BET inhibitor. Molecular docking indicated high-affinity binding of the proteins encoded by these genes with JQ1. In conclusion, our study reveals the crucial role of activated DCs in ccRCC, offering new insights into predicting immune response, targeted therapy effectiveness, and prognosis for ccRCC patients.
树突状细胞 (DCs) 作为肿瘤免疫的关键调节因子，激活的 DC 通过分泌促炎细胞因子和表达共刺激分子来增强抗肿瘤反应。大多数当前的研究都集中在 DC 亚群与透明细胞肾细胞癌 (ccRCC) 之间的关系上，但从免疫激活的角度研究 DC 与 ccRCC 之间的联系有限。在这项研究中，在 bulk 和单细胞 RNA-seq 数据中鉴定了激活的 DC 基因。使用单变量、多变量 Cox 回归和 LASSO 回归构建了与激活的 DC 相关的预后模型。该预后模型在三个外部验证集：GSE167573、ICGC 和 E-MTAB-1980 中进行了验证。该预后模型由五个基因组成， 、 、 、 、 。使用 qRT-PCR 在组织样本中验证了这些基因的表达。分层分析表明，该预后模型能够更好地预测晚期 ccRCC 患者的结局。风险评分与肿瘤进展、肿瘤突变负担、免疫细胞浸润和免疫治疗不良结局相关。值得注意的是，这五个基因的表达与 BET 抑制剂 JQ1 的敏感性之间存在很强的相关性。分子对接表明这些基因编码的蛋白质与 JQ1 具有高亲和力结合。总之，我们的研究揭示了激活的 DC 在 ccRCC 中的关键作用，为预测免疫反应、靶向治疗效果和 ccRCC 患者的预后提供了新的见解。
