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pmid:35463956

Development and Validation of Novel Prognostic Models for Immune-Related Genes in Osteosarcoma.

Junqing Li · Li Su · Xing Xiao · Feiran Wu · Guijuan Du · Xinjun Guo · Fanguo Kong · Jie Yao · Huimin Zhu

Frontiers in molecular biosciences · 2022 doi:10.3389/fmolb.2022.828886

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Experiment

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Data

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Analysis

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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
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title
Development and Validation of Novel Prognostic Models for Immune-Related Genes in Osteosarcoma.
doi
10.3389/fmolb.2022.828886
pmid
35463956
authors array · 9 items
[0]
Junqing Li
[1]
Li Su
[2]
Xing Xiao
[3]
Feiran Wu
[4]
Guijuan Du
[5]
Xinjun Guo
[6]
Fanguo Kong
[7]
Jie Yao
[8]
Huimin Zhu
journal
Frontiers in molecular biosciences
year
2022
abstract
Immunotherapy has shown excellent therapeutic effects on various malignant tumors; however, to date, immunotherapy for osteosarcoma is still suboptimal. In this study, we performed comprehensive bioinformatic analysis of immune-related genes (IRGs) and tumor-infiltrating immune cells (TIICs). Datasets of differentially expressed IRGs were extracted from the GEO database (GSE16088). The functions and prognostic values of these differentially expressed IRGs were systematically investigated using a series of bioinformatics methods. In addition, CCK8 and plate clone formation assays were used to explore the effect of PGF on osteosarcoma cells, and twenty-nine differentially expressed IRGs were identified, of which 95 were upregulated and 34 were downregulated. Next, PPI was established for Identifying Hub genes and biology networks by Cytoscape. Six IRGs (APLNR, TPM2, PGF, CD86, PROCR, and SEMA4D) were used to develop an overall survival (OS) prediction model, and two IRGs (HLA-B and PGF) were used to develop a relapse-free survival (RFS) prediction model. Compared with the low-risk patients in the training cohort (GSE39058) and TARGET validation cohorts, high-risk patients had poorer OS and RFS. Using these identified IRGs, we used OS and RFS prediction nomograms to generate a clinical utility model. The risk scores of the two prediction models were associated with the infiltration proportions of some TIICs, and the activation of memory CD4 T-cells was associated with OS and RFS. CD86 was associated with CTLA4 and CD28 and influenced the infiltration of different TIICs. In vitro experiments showed that the knockdown of PGF inhibited the proliferation and viability of osteosarcoma cells. In conclusion, these findings help us better understand the prognostic roles of IRGs and TIICs in osteosarcoma, and CD86 and PGF may serve as specific immune targets.
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To further evaluate the prognostic utility of these IRGs, we subsequently performed a time-dependent ROC analysis
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To further evaluate the prognostic utility of these IRGs, we subsequently performed a time-dependent ROC analysis
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Six IRGs (APLNR, TPM2, PGF, CD86, PROCR, and SEMA4D) were used to develop an overall survival (OS) prediction model, and two IRGs (HLA-B and PGF) were used to develop a relapse-free survival (RFS) prediction model.
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Six IRGs (APLNR, TPM2, PGF, CD86, PROCR, and SEMA4D) were used to develop an overall survival (OS) prediction model, and two IRGs (HLA-B and PGF) were used to develop a relapse-free survival (RFS) prediction model.
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Six IRGs (APLNR, TPM2, PGF, CD86, PROCR, and SEMA4D) were used to develop an overall survival (OS) prediction model, and two IRGs (HLA-B and PGF) were used to develop a relapse-free survival (RFS) prediction model.
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asset:data:geo:GSE16088 licence not read
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TIICs. In vitro experiments showed that the knockdown of PGF inhibited the proliferation and viabi
[1]
urvival was 10 years. Cell Culture and siRNA Transfection MG63 and U2OS cell lines were purchased from
[2]
n of survival was 10 years. Cell Culture and siRNA Transfection MG63 and U2OS cell lines were p
[3]
37°C in an atmosphere of 5% CO2. GenOFF PGF siRNA and negative control siRNA oligonucleotides
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tatistical analyses in this study, including RNA-seq data normalization and transformation, CIBER
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et al., 2018). The training cohort underwent RNA sequencing, and clinical datasets were extracted from G
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(Shanghai, China). MG63 and U2OS cells were cultured in DMEM (Biological Industries, Shanghai, China
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Cell Culture and siRNA Transfection MG63 and U2OS cell lines were purchased from the Cell Bank
[2]
demy of Sciences (Shanghai, China). MG63 and U2OS cells were cultured in DMEM (Biological Indu
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Complete file
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In this study, we performed comprehensive bioinformatic analysis of immune-related genes (IRGs) and tumor-infiltrating immune cells (TIICs). Datasets of differentially expressed IRGs were extracted from the GEO database (GSE16088). The functions and prognostic values of these differentially expressed IRGs were systematically investigated using a series of bioinformatics methods. In addition, CCK8 and plate clone formation assays were used to explore the effect of PGF on osteosarcoma cells, and twenty-nine differentially expressed IRGs were identified, of which 95 were upregulated and 34 were downregulated. Next, PPI was established for Identifying Hub genes and biology networks by Cytoscape. Six IRGs (APLNR, TPM2, PGF, CD86, PROCR, and SEMA4D) were used to develop an overall survival (OS) prediction model, and two IRGs (HLA-B and PGF) were used to develop a relapse-free survival (RFS) prediction model. Compared with the low-risk patients in the training cohort (GSE39058) and TARGET validation cohorts, high-risk patients had poorer OS and RFS. Using these identified IRGs, we used OS and RFS prediction nomograms to generate a clinical utility model. The risk scores of the two prediction models were associated with the infiltration proportions of some TIICs, and the activation of memory CD4 T-cells was associated with OS and RFS. CD86 was associated with CTLA4 and CD28 and influenced the infiltration of different TIICs. In vitro experiments showed that the knockdown of PGF inhibited the proliferation and viability of osteosarcoma cells. 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In addition, CCK8 and plate clone formation assays were used t"], "order_basis": "paper_text_order:599", "id": "assay:1"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["TIICs. In vitro experiments showed that the knockdown of PGF inhibited the proliferation and viabi", "urvival was 10 years. Cell Culture and siRNA Transfection MG63 and U2OS cell lines were purchased from", "n of survival was 10 years. Cell Culture and siRNA Transfection MG63 and U2OS cell lines were p", "37°C in an atmosphere of 5% CO2. 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MG63 and U2OS cells were cultured in DMEM (Biological Industries, Shanghai, China", "Cell Culture and siRNA Transfection MG63 and U2OS cell lines were purchased from the Cell Bank", "demy of Sciences (Shanghai, China). MG63 and U2OS cells were cultured in DMEM (Biological Indu"], "order_basis": "paper_text_order:3077", "id": "assay:4"}, {"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["cox_ph"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["To further evaluate the prognostic utility of these IRGs, we subsequently performed a time-dependent ROC analysis"], "order_basis": "consumes_earlier_output", "id": "assay:5"}]}