PMID- 37070095
OWN - NLM
STAT- MEDLINE
DCOM- 20230419
LR  - 20231102
IS  - 2167-8359 (Electronic)
IS  - 2167-8359 (Linking)
VI  - 11
DP  - 2023
TI  - Exploring the role of differentially expressed metabolic genes and their 
      mechanisms in bone metastatic prostate cancer.
PG  - e15013
LID - 10.7717/peerj.15013 [doi]
LID - e15013
AB  - BACKGROUND: Approximately 10-20% of patients diagnosed with prostate cancer (PCa) 
      evolve into castration-resistant prostate cancer (CRPC), while nearly 90% of 
      patients with metastatic CRPC (mCRPC) exhibit osseous metastases (BM). These BM 
      are intimately correlated with the stability of the tumour microenvironment. 
      PURPOSE: This study aspires to uncover the metabolism-related genes and the 
      underlying mechanisms responsible for bone metastatic prostate cancer (BMPCa). 
      METHODS: Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) 
      datasets of PCa and BM were analyzed through R Studio software to identify 
      differentially expressed genes (DEGs). The DEGs underwent functional enrichment 
      via Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO), with 
      key factors screened by a random forest utilized to establish a prognostic model 
      for PCa. The study explored the relationship between DEGs and the stability of 
      the immune microenvironment. The action and specificity of CRISP3 in PCa was 
      validated through western blot analysis, CCK-8 assay, scratch assay, and cellular 
      assay. RESULTS: The screening of GEO and TCGA datasets resulted in the 
      identification of 199 co-differential genes. Three DEGs, including DES, HBB, and 
      SLPI, were selected by random forest classification model and cox regression 
      model. Immuno-infiltration analysis disclosed that a higher infiltration of naive 
      B cells and resting CD4 memory T cells occurred in the high-expression group of 
      DES, whereas infiltration of resting M1 macrophages and NK cells was greater in 
      the low-expression group of DES. A significant infiltration of neutrophils was 
      observed in the high-expression group of HBB, while greater infiltration of gamma 
      delta T cells and M1 macrophages was noted in the low-expression group of HBB. 
      Resting dendritic cells, CD8 T cells, and resting T regulatory cells (Tregs) 
      infiltrated significantly in the high-expression group of SLPI, while only 
      resting mast cells infiltrated significantly in the low-expression group of SLPI. 
      CRISP3 was established as a critical gene in BMPCa linked to DES expression. 
      Targeting CRISP3, d-glucopyranose may impact tumour prognosis. During the 
      mechanistic experiments, it was established that CRISP3 can advance the 
      proliferation and metastatic potential of PCa by advancing 
      epithelial-to-mesenchymal transition (EMT). CONCLUSION: By modulating lipid 
      metabolism and maintaining immunological and microenvironmental balance, DES, 
      HBB, and SLPI suppress prostate cancer cell growth. The presence of 
      DES-associated CRISP3 is a harbinger of unfavorable outcomes in prostate cancer 
      and may escalate tumor proliferation and metastatic capabilities by inducing 
      epithelial-mesenchymal transition.
CI  - (c)2023 Zhang et al.
FAU - Zhang, Qingfu
AU  - Zhang Q
AD  - Department of Urology, Tai 'an Central Hospital, Tai 'an, Shandong, China.
FAU - Zhang, Peng
AU  - Zhang P
AD  - Department of Spine Surgery, Tai 'an Central Hospital, Tai 'an, Shandong, China.
FAU - Zhao, Zhongting
AU  - Zhao Z
AD  - Department of Spinal Surgery, The Third People's Hospital of Jinan, Jinan, 
      Shandong, China.
FAU - Wang, Jun
AU  - Wang J
AD  - Department of Emergency, Qingdao Eighth People's Hospital, Qingdao, China.
FAU - Zhang, Hepeng
AU  - Zhang H
AD  - Department of Urology, Tai 'an Central Hospital, Tai 'an, Shandong, China.
LA  - eng
PT  - Journal Article
DEP - 20230412
PL  - United States
TA  - PeerJ
JT  - PeerJ
JID - 101603425
SB  - IM
MH  - Male
MH  - Humans
MH  - *Prostatic Neoplasms, Castration-Resistant/genetics
MH  - Prostate
MH  - *Bone Neoplasms/genetics
MH  - Lipid Metabolism
MH  - B-Lymphocytes
MH  - Tumor Microenvironment/genetics
PMC - PMC10105558
OTO - NOTNLM
OT  - Bone metastasis (BM)
OT  - Epithelial to mesenchymal transition (EMT)
OT  - Immuno-microenvironmental homeostasis
OT  - Prostate cancer (PCa)
OT  - scRNA-seq
COIS- The authors declare there are no competing interests.
EDAT- 2023/04/19 06:00
MHDA- 2023/04/19 06:41
PMCR- 2023/04/12
CRDT- 2023/04/18 01:47
PHST- 2023/01/13 00:00 [received]
PHST- 2023/02/16 00:00 [accepted]
PHST- 2023/04/19 06:41 [medline]
PHST- 2023/04/18 01:47 [entrez]
PHST- 2023/04/19 06:00 [pubmed]
PHST- 2023/04/12 00:00 [pmc-release]
AID - 15013 [pii]
AID - 10.7717/peerj.15013 [doi]
PST - epublish
SO  - PeerJ. 2023 Apr 12;11:e15013. doi: 10.7717/peerj.15013. eCollection 2023.