PMID- 38515694
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240323
IS  - 2405-8440 (Print)
IS  - 2405-8440 (Electronic)
IS  - 2405-8440 (Linking)
VI  - 10
IP  - 6
DP  - 2024 Mar 30
TI  - Immunogenic cell death related mRNAs associated signature to predict 
      immunotherapeutic response in osteosarcoma.
PG  - e27630
LID - 10.1016/j.heliyon.2024.e27630 [doi]
LID - e27630
AB  - BACKGROUND: Immunogenic cell death (ICD) is related to cancer prognosis, which 
      has a synergic effect in combination with chemotherapy or immunotherapy. Yet, the 
      relationship between ICD and osteosarcoma remained unclear. MATERIALS AND 
      METHODS: Three osteosarcoma datasets including therapeutically applicable 
      research to generate effective treatments (TARGET), GSE126209 and GSE21257 
      datasets were included. A protein-protein interaction network was constructed 
      based on ICD-related genes. We performed unsupervised consensus clustering to 
      classify molecular subtypes (clusters). Survival analysis, Estimation of stromal 
      and immune cells in malignant tumour tissues using expression data (ESTIMATE), 
      Cell-type identification by estimating relative subsets of RNA transcripts 
      (CIBERSORT), and differential analysis were employed to characterize the 
      molecular differences between different clusters. Univariate Cox regression 
      analysis was conducted to confirm prognostic genes. Quantitative reverse 
      transcription polymerase chain reaction (qRT-PCR) was used to demonstrate the 
      aberrant expression of ICD-correlated signature genes in osteosarcoma. A series 
      of cellular experiments, including cell counting kit-8 (CCK-8), transwell, and 
      flow cytometry, were used to demonstrate the regulatory role of key genes in the 
      ICD model on the malignant phenotype of osteosarcoma. RESULTS: Three clusters 
      (cluster1, 2, 3) were constructed and they showed distinct overall survival and 
      immune infiltration. ICD-related genes were highly expressed in cluster1. 
      Moreover, Cluster1 had the best prognosis, high immune score and high expression 
      of human leukocyte antigen (HLA)-related genes. TLR4, LY96, IFNGR1, CD4, and 
      CASP1 were identified as prognostic genes for establishing an ICD-related risk 
      signature. According to the risk signature, two risk groups (high and low risks) 
      showing differential prognosis and response to immunotherapy. The low risks group 
      had a better prognosis but was not sensitive to immunotherapy. Molecular assays 
      verified that prognostic genes were abnormally under-expressed in osteosarcoma. 
      Cellular assays demonstrated that LY96, the most significantly down-regulated 
      gene in osteosarcoma, inhibited the migration, invasion, and proliferation 
      phenotypes of osteosarcoma cells and prolonged the cell cycle. Analysis of 
      oxidative stress related pathway enrichment in tumor microenvironment was 
      conducted by single-sample gene set enrichment analysis (ssGSEA). CONCLUSIONS: 
      This study demonstrated the prognostic significance of ICD-correlated genes in 
      osteosarcoma patients. The five-gene risk signature facilitate prognostic 
      evaluation and prediction of osteosarcoma patients' response to immunotherapy. 
      The risk signature also offered a possibility for the exploit of novel 
      ICD-related treatment.
CI  - (c) 2024 The Authors.
FAU - Han, Shuai
AU  - Han S
AD  - Department of Orthopedics, Shanghai Pudong New Area People's Hospital, Shanghai, 
      201299, China.
FAU - Wang, Qinghe
AU  - Wang Q
AD  - Department of Orthopedics, Shanghai Pudong New Area People's Hospital, Shanghai, 
      201299, China.
FAU - Shen, Mingquan
AU  - Shen M
AD  - Department of Orthopedics, Shanghai Pudong New Area People's Hospital, Shanghai, 
      201299, China.
FAU - Zhang, Xingpeng
AU  - Zhang X
AD  - Department of Orthopedics, Shanghai Pudong New Area People's Hospital, Shanghai, 
      201299, China.
FAU - Wang, Jian
AU  - Wang J
AD  - Department of Orthopedics, Shanghai Pudong New Area People's Hospital, Shanghai, 
      201299, China.
LA  - eng
PT  - Journal Article
DEP - 20240309
PL  - England
TA  - Heliyon
JT  - Heliyon
JID - 101672560
PMC - PMC10955266
OTO - NOTNLM
OT  - Immunogenic cell death
OT  - Osteosarcoma
OT  - Oxidative stress
OT  - Risk signature
OT  - Tumor microenvironment
COIS- The authors declare that they have no known competing financial interests or 
      personal relationships that could have appeared to influence the work reported in 
      this paper.
EDAT- 2024/03/22 06:44
MHDA- 2024/03/22 06:45
PMCR- 2024/03/09
CRDT- 2024/03/22 03:58
PHST- 2023/12/04 00:00 [received]
PHST- 2024/03/03 00:00 [revised]
PHST- 2024/03/04 00:00 [accepted]
PHST- 2024/03/22 06:45 [medline]
PHST- 2024/03/22 06:44 [pubmed]
PHST- 2024/03/22 03:58 [entrez]
PHST- 2024/03/09 00:00 [pmc-release]
AID - S2405-8440(24)03661-2 [pii]
AID - e27630 [pii]
AID - 10.1016/j.heliyon.2024.e27630 [doi]
PST - epublish
SO  - Heliyon. 2024 Mar 9;10(6):e27630. doi: 10.1016/j.heliyon.2024.e27630. eCollection 
      2024 Mar 30.