Identification of a novel eighteen-gene signature of recurrent metastasis neuroblastoma
Identification of a novel eighteen-gene signature of recurrent metastasis neuroblastoma
复制标题
DOI：
10.1007/s00109-023-02299-3
复制
发表时间：
2023-03
期刊：
影响因子：
--
通讯作者：
Shufan Zhang;Rongjiang Jiang;Manqiu Yang;Tao Wang;Hui Chen;Yifan Shi;Wei Liu;Moli Huang
中科院分区：
文献类型：
--
作者：
Shufan Zhang;Rongjiang Jiang;Manqiu Yang;Tao Wang;Hui Chen;Yifan Shi;Wei Liu;Moli Huang
神经母细胞瘤是儿童期最常见的恶性肿瘤，30%以上的患者发生转移。复发转移是神经母细胞瘤预后不良和死亡率高的主要原因。对此，目前仍缺乏足够的生物标志物和有效的治疗方法。因此，我们对神经母细胞瘤患者进行了多组学分析，以产生有效治疗的治疗应用研究 (TARGET)。根据临床复发部位信息，将来自原发部位的肿瘤样本分为复发转移组和原发肿瘤组。通过比较RNA-Seq和拷贝数变异差异获得初始基因特征。生存数据用于进一步筛选预后相关基因。这个 18 基因特征由三个簇组成：肿瘤抑制、细胞增殖和免疫。超级增强子与 IRF3 一起参与 cluster2 中 NCAPG 的表达增强。根据原发性神经母细胞瘤中的基因特征表达，可以在肿瘤转移发生之前对其进行预测。根据癌症药物敏感性基因组学（GDSC）的抗癌药物数据集，预计长春瑞滨和多西他赛对复发性转移性神经母细胞瘤具有高敏感性。总之，我们的研究提供了一种新的转移生物标志物，有助于理解肿瘤复发转移的机制。关键信息我们鉴定了复发转移神经母细胞瘤的新十八基因特征，并建立了风险和分类模型。我们剖析了 NCAPG 在特征中的调节作用。我们发现复发转移中的免疫耗竭和免疫抑制 神经母细胞瘤。预计长春瑞滨和多西他赛对复发性转移性神经母细胞瘤具有高度敏感性。
Neuroblastoma is the most common malignant tumor in childhood, and metastases occur in more than 30% patients. Recurrent metastasis is the main cause of poor prognosis and high mortality in neuroblastoma. In this regard, there is still a lack of sufficient biomarkers and effective therapies. Therefore, we performed a multi-omics analysis of neuroblastoma patients from Therapeutically Applicable Research To Generate Effective Treatments (TARGET). With clinical relapse site information, tumor samples derived from the primary site were divided into recurrent metastasis and primary tumor groups. The initial gene signature was obtained by comparing RNA-Seq and copy number variation differences. Survival data was used to further filter prognosis-related genes. This 18-gene signature consists of three clusters: tumor suppression, cell proliferation, and immunity. A super enhancer is involved in the enhanced expression ofNCAPGin cluster2 together with IRF3. Based on the gene signature expression in primary neuroblastoma, it is possible to predict tumor metastasis before it occurs. According to the anticancer drug dataset of Genomics of Drug Sensitivity in Cancer (GDSC), vinorelbine and docetaxel were predicted to have high sensitivity against recurrent metastatic neuroblastoma. In conclusion, our study offers a novel metastasis biomarker and helps understand the mechanisms of tumor recurrent metastasis.Key messagesWe identified a novel eighteen-gene signature of recurrent metastasis neuroblastoma and build risk and classification models.We dissected the regulatory role of NCAPG in signatures.We found immune exhaustion and immunosuppression in recurrent metastasis neuroblastoma.Vinorelbine and docetaxel were predicted to have high sensitivity against recurrent metastatic neuroblastoma.