Chen Jiangtao, Zhai Xiao, Kuang Haiyang, Zhang Ai
Department of Pediatrics, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Sci Rep. 2025 May 23;15(1):17885. doi: 10.1038/s41598-025-02661-0.
Neuroblastoma (NB) is the most common type of pediatric extra-cranial tumor that arises in the sympathetic nervous system. The heterogeneity of T-cell exhaustion (TEX) has been linked to the determination of distinct clinical outcomes and the effectiveness of immunotherapy in numerous adult malignancies. Therefore, studying the heterogeneous TEX landscape in NB as well as its impact on clinical outcomes is meaningful. The gene expression and clinical datasets of the Sequencing Quality Control (SEQC), E-MTAB-8248, and Therapeutically Applicable Research to Generate Effective Treatments (TARGET) cohorts were downloaded from publicly available databases. Two TEX-related clusters for neuroblastoma were identified in the SEQC cohort. Patients in TEX-C1 exhibited superior overall survival (OS) and event-free survival (EFS) rates compared with those in TEX-C2. And TEX-C1 had more immune cells infiltrating, as well as higher expression of immune checkpoint genes. A total of 1984 genes were differentially expressed between these two clusters, of which 1712 were associated with OS. A gene signature consisting of ten TEX-related genes was developed, and a risk score was computed for each patient. Based on the risk score, SEQC patients were split into high- and low-risk groups with significantly different survival rates. The risk score was an independent risk factor predicting survival and showed superior prediction power for 3, 5, and 10-year survival compared to individual clinical parameters. The signature was further confirmed in the TARGET and E-MTAB-8248 cohorts. This study has successfully constructed a risk score model for NB prognosis, utilizing TEX as its foundation. The model provides risk classification and survival evaluation, which can further guide treatment.
神经母细胞瘤（NB）是最常见的起源于交感神经系统的小儿颅外肿瘤。T细胞耗竭（TEX）的异质性与多种成人恶性肿瘤中不同临床结局的判定及免疫治疗的有效性相关。因此，研究NB中异质性的TEX格局及其对临床结局的影响具有重要意义。从公开可用数据库下载了测序质量控制（SEQC）、E-MTAB-8248和生成有效治疗方法的治疗应用研究（TARGET）队列的基因表达和临床数据集。在SEQC队列中鉴定出两个与神经母细胞瘤相关的TEX簇。与TEX-C2中的患者相比，TEX-C1中的患者表现出更好的总生存期（OS）和无事件生存期（EFS）率。并且TEX-C1有更多的免疫细胞浸润，以及更高的免疫检查点基因表达。这两个簇之间共有1984个基因差异表达，其中1712个与OS相关。开发了一个由十个与TEX相关的基因组成的基因特征，并为每位患者计算了一个风险评分。基于风险评分，SEQC患者被分为高风险组和低风险组，生存率有显著差异。风险评分是预测生存的独立风险因素，与个体临床参数相比，对3年、5年和10年生存显示出更好的预测能力。该特征在TARGET和E-MTAB-8248队列中得到进一步证实。本研究成功构建了一个以TEX为基础的NB预后风险评分模型。该模型提供风险分类和生存评估，可进一步指导治疗。
