PMID- 38019470
OWN - NLM
STAT- MEDLINE
DCOM- 20231207
LR  - 20231217
IS  - 1945-4589 (Electronic)
IS  - 1945-4589 (Linking)
VI  - 15
IP  - 22
DP  - 2023 Nov 27
TI  - Immune microenvironment heterogeneity reveals distinct subtypes in neuroblastoma: 
      insights into prognosis and therapeutic targets.
PG  - 13345-13367
LID - 10.18632/aging.205246 [doi]
AB  - BACKGROUND: Neuroblastoma (NB) is a childhood cancer originating from immature 
      nerve cells in the sympathetic nervous system. Current clinical and molecular 
      subtyping methods for NB have limitations in providing accurate prognostic 
      information and guiding treatment decisions. RESULTS: To overcome these 
      challenges, we explored the microenvironment of NB based on the knowledge-based 
      functional gene expression signatures (Fges), which revealed heterogeneous 
      subtypes. Consensus clustering of Fges activity scores identified three subtypes 
      (Cluster 1, Cluster 2, and Cluster 3) that demonstrated significant differences 
      in prognosis compared to mainstream subtypes. We assessed the immune 
      infiltration, immunogenicity, CD8T cytotoxicity, and tumor purity of these 
      subtypes, uncovering their distinct biological functions. Cluster 1 and Cluster 2 
      exhibited higher immunoreactivity, while Cluster 3 displayed higher tumor purity 
      and poor prognosis. Gene ontology annotation and pathway analysis identified 
      immune activation in Cluster 1, epithelial-mesenchymal transition (EMT) in 
      Cluster 2, and cell cycle processes in Cluster 3. Notably, the impact of EMT 
      activity on prognosis may vary across NB subtypes. A classification model using 
      XGBoost accurately predicted subtypes in independent NB cohorts, with significant 
      prognostic differences. GPR125, CDK4, and GREB1 emerged as potential therapeutic 
      targets in Cluster 3. CD4K inhibitors showed subtype-specific responses, 
      suggesting tailored treatment strategies. Single-cell analysis highlighted 
      unfavorable clinical features in Cluster 3, including high-risk classification 
      and reduced cytotoxicity. Suppressed interactions between monocytes, macrophages, 
      and regulatory T cells were observed, affecting immune regulation and patient 
      prognosis. CONCLUSION: To summarize, we have identified a new independent 
      prognostic factor in NB that underscores the significant correlation between 
      tumor phenotype and immune contexture. These findings deepen our understanding of 
      NB subtypes and immune cell interactions, paving the way for more effective 
      treatment approaches.
FAU - Yang, Yanlan
AU  - Yang Y
AD  - Department of Hematology and Oncology, Shenzhen Children’s Hospital, 
      Shenzhen, Guangdong, PR China.
FAU - Li, Huamei
AU  - Li H
AD  - Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital, Medical 
      School, Nanjing University, Nanjing 210008, PR China.
FAU - Zheng, Donghui
AU  - Zheng D
AD  - Department of Hematology and Oncology, Shenzhen Children’s Hospital, 
      Shenzhen, Guangdong, PR China.
FAU - Li, Xuemei
AU  - Li X
AD  - Department of Hematology and Oncology, Shenzhen Children’s Hospital, 
      Shenzhen, Guangdong, PR China.
FAU - Liu, Hongyan
AU  - Liu H
AD  - Department of Hematology and Oncology, Shenzhen Children’s Hospital, 
      Shenzhen, Guangdong, PR China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20231127
PL  - United States
TA  - Aging (Albany NY)
JT  - Aging
JID - 101508617
SB  - IM
MH  - Humans
MH  - Child
MH  - Prognosis
MH  - *Neuroblastoma/metabolism
MH  - Treatment Outcome
MH  - Epithelial-Mesenchymal Transition
MH  - Transcriptome
MH  - Tumor Microenvironment/genetics
PMC - PMC10713432
OTO - NOTNLM
OT  - drug response
OT  - neuroblastoma
OT  - prognosis
OT  - subtypes
OT  - tumor microenvironment
COIS- CONFLICTS OF INTEREST: The authors declare no conflicts of interest related to 
      this study.
EDAT- 2023/11/29 12:42
MHDA- 2023/12/07 12:42
PMCR- 2023/11/30
CRDT- 2023/11/29 11:13
PHST- 2023/07/11 00:00 [received]
PHST- 2023/10/23 00:00 [accepted]
PHST- 2023/12/07 12:42 [medline]
PHST- 2023/11/29 12:42 [pubmed]
PHST- 2023/11/29 11:13 [entrez]
PHST- 2023/11/30 00:00 [pmc-release]
AID - 205246 [pii]
AID - 10.18632/aging.205246 [doi]
PST - ppublish
SO  - Aging (Albany NY). 2023 Nov 27;15(22):13345-13367. doi: 10.18632/aging.205246. 
      Epub 2023 Nov 27.