Abstract 518P
Background
Different levels of evidences have demonstrated programmed cell death (PCD) were significantly associated with the development, prognosis and tumor microenvironment (TME) of cancer. No studies have explored the PCD patterns for neuroblastoma.
Methods
Here, we collected neuroblastoma transcriptome and clinical data from public databases and performed integrated analysis to dissect the PCD patterns and their roles in prognosis, clinical and molecular characteristics and TME.
Results
We identified three neuroblastoma subtypes with different PCD patterns: cluster 1 characterized by highest ferroptosis score, necroptosis score and pyroptosis score, cluster 2 with best survival characterized by highest autophagy score, and cluster 3 with worst survival characterized by highest apoptosis score. The clinical and molecular characteristic of three PCD subtypes were consistent with clinical knowledge. The sensitivity of three PCD subtypes to chemotherapeutic drugs was opposite to survival results, which might be attributed to the difference in neuroblastoma differentiation. Analyses of TME indicated cluster 1 had an immune-hot TME and cluster 3 had an immune-cold TME. The distribution of MYCN expression was lowest in cluster1 and highest in cluster 3 which was completely opposite to TME and score of known immunogenic cell death including necroptosis and pyroptosis. We speculated MYCN might regulate immunogenic cell death and cancer immunity to affect the development and prognosis of neuroblastoma.
Conclusions
The correlation among MYCN, immunogenic cell death and TME could provide a novel insight to immune checkpoint inhibitor monotherapy or combination of immunogenic cell death induced drugs and immune therapy, to potentiate the efficacy and improve the prognosis of neuroblastoma with a certain PCD patterns.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The author.
Funding
Has not received any funding.
Disclosure
The author has declared no conflicts of interest.