PMID- 36199426
OWN - NLM
STAT- MEDLINE
DCOM- 20221007
LR  - 20231101
IS  - 1942-0994 (Electronic)
IS  - 1942-0900 (Print)
IS  - 1942-0994 (Linking)
VI  - 2022
DP  - 2022
TI  - Bulk and Single-Cell Transcriptome Analyses Revealed That the Pyroptosis of 
      Glioma-Associated Macrophages Participates in Tumor Progression and 
      Immunosuppression.
PG  - 1803544
LID - 10.1155/2022/1803544 [doi]
LID - 1803544
AB  - Glioma is the most common of all central nervous system (CNS) malignancies and is 
      associated with a poor prognosis. Pyroptosis has been proven to be associated 
      with the progression of multiple tumors and CNS diseases. However, the 
      relationships between pyroptosis and clinical prognosis and immune cell 
      infiltration are unclear in glioma. In this study, we conducted a comprehensive 
      exploration of pyroptosis in glioma. First, prognosis-related genes were screened 
      at each key regulatory locus in the pyroptosis pathway, and the prognostic 
      ability and coexpression relationships of GSDMD and its upstream pathway genes 
      NLRC4/CASP1/CASP4 were identified and well validated in multiple datasets. Tissue 
      microarray-based immunohistochemistry results showed higher levels of NLRC4 and 
      N-terminal GSDMD in high-grade gliomas, providing conclusive evidence of 
      pyroptosis in gliomas. The robustness of the prognostic model based on these four 
      genes was well validated in TCGA and CGGA cohorts. Bulk RNA-seq-based analysis 
      showed that the group defined as the high-risk group according to the model 
      showed activation of multiple inflammatory response pathways and impaired 
      synaptic gene expression and had a higher infiltration of bone marrow-derived 
      macrophages (BMDMs) and a hypersuppressed immune microenvironment. More 
      importantly, three independent single-cell RNA-seq (scRNA-seq) datasets 
      demonstrated that tumor-infiltrating macrophages, particularly BMDMs but not 
      tissue-resident microglia, showed significant coexpression of the GSDMD and CASP 
      genes, and BMDMs from high-grade gliomas accounted for a higher proportion of 
      immune infiltrating cells and had higher expression of pyroptosis genes. Finally, 
      we revealed the activation of pathways in response to LPS/bacteria and oxidative 
      stress during BMDM development toward the pyroptosis cell fate by pseudotime 
      trajectory analysis, suggesting potential BMDM pyroptosis initiators. The above 
      results provide not only novel insights into the pathological mechanisms of 
      glioma but also novel therapeutic targets for glioma, suggesting the potential 
      application of pyroptosis inhibitors (e.g., disulfiram).
CI  - Copyright (c) 2022 Lin Li et al.
FAU - Li, Lin
AU  - Li L
AD  - The State Key Laboratory of Pharmaceutical Biotechnology, School of Life 
      Sciences, Nanjing University, Nanjing, China.
FAU - Wu, Leyang
AU  - Wu L
AD  - The State Key Laboratory of Pharmaceutical Biotechnology, School of Life 
      Sciences, Nanjing University, Nanjing, China.
AD  - Changzhou High-Tech Research Institute of Nanjing University and Jiangsu Target 
      Pharma Laboratories Inc., Changzhou, China.
FAU - Yin, Xingpeng
AU  - Yin X
AD  - The State Key Laboratory of Pharmaceutical Biotechnology, School of Life 
      Sciences, Nanjing University, Nanjing, China.
FAU - Li, Chenyang
AU  - Li C
AD  - The State Key Laboratory of Pharmaceutical Biotechnology, School of Life 
      Sciences, Nanjing University, Nanjing, China.
FAU - Hua, Zichun
AU  - Hua Z
AUID- ORCID: 0000-0001-7962-0402
AD  - The State Key Laboratory of Pharmaceutical Biotechnology, School of Life 
      Sciences, Nanjing University, Nanjing, China.
AD  - Changzhou High-Tech Research Institute of Nanjing University and Jiangsu Target 
      Pharma Laboratories Inc., Changzhou, China.
AD  - School of Biopharmacy, China Pharmaceutical University, Nanjing, China.
LA  - eng
PT  - Journal Article
DEP - 20220926
PL  - United States
TA  - Oxid Med Cell Longev
JT  - Oxidative medicine and cellular longevity
JID - 101479826
RN  - 0 (Lipopolysaccharides)
RN  - TR3MLJ1UAI (Disulfiram)
SB  - IM
MH  - Disulfiram
MH  - Gene Expression Profiling
MH  - *Glioma/metabolism
MH  - Humans
MH  - Immunosuppression Therapy
MH  - Lipopolysaccharides/metabolism
MH  - Macrophages/metabolism
MH  - *Pyroptosis/genetics
MH  - Single-Cell Analysis
MH  - Tumor Microenvironment
PMC - PMC9529448
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/10/07 06:00
MHDA- 2022/10/12 06:00
PMCR- 2022/09/26
CRDT- 2022/10/06 02:06
PHST- 2022/06/15 00:00 [received]
PHST- 2022/08/13 00:00 [revised]
PHST- 2022/08/31 00:00 [accepted]
PHST- 2022/10/06 02:06 [entrez]
PHST- 2022/10/07 06:00 [pubmed]
PHST- 2022/10/12 06:00 [medline]
PHST- 2022/09/26 00:00 [pmc-release]
AID - 10.1155/2022/1803544 [doi]
PST - epublish
SO  - Oxid Med Cell Longev. 2022 Sep 26;2022:1803544. doi: 10.1155/2022/1803544. 
      eCollection 2022.