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Identification of a novel eighteen-gene signature of recurrent metastasis neuroblastoma.

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 of NCAPG in 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 MESSAGES: We 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.

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