Characterization of the Tumor Microenvironment in Osteosarcoma Identifies Prognostic- and Immunotherapy-Relevant Gene Signatures.

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Thus, microenvironment-targeted strategies are urgently needed to improve OS treatment outcomes. Using principal component analysis (PCA), we systematically examined the tumor microenvironment (TME) and immune cell infiltration of 88 OS cases and constructed a TME scoring system based on the TMEscore high and TMEscore low phenotypes. Our analysis revealed that TMEscore high correlates with longer survival in OS patients, elevated immune cell infiltration, increased immune checkpoints, and increased sensitivity to chemotherapy. TMEscore low strongly correlated with immune exclusion. These observations were externally validated using a GEO dataset (GSE21257) from 53 OS patients. Our laboratory data also proved our findings. This finding enhances our understanding of the immunological landscape in OS and may uncover novel targeted therapeutic strategies.", "claims": [{"id": "claim-method", "statement": "Using principal component analysis (PCA), we systematically examined the tumor microenvironment (TME) and immune cell infiltration of 88 OS cases and constructed a TME scoring system based on the TMEscore high and TMEscore low phenotypes.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36065454", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Using principal component analysis (PCA), we systematically examined the tumor microenvironment (TME) and immune cell infiltration of 88 OS cases and constructed a TME scoring system based on the TMEscore high and TMEscore low phenotypes."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All datasets are available from TCGA database (https://portal.gdc.cancer.gov/projects/TARGET-OS) and GEO database (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE21257).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36065454", "locator": "sections[34] \"Data Availability\" paragraph 2", "quote": "All datasets are available from TCGA database (https://portal.gdc.cancer.gov/projects/TARGET-OS) and GEO database (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE21257)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "TMEscore high correlates with longer survival in OS patients, elevated immune cell infiltration, increased immune checkpoints, and increased sensitivity to chemotherapy.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36065454", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Our analysis revealed that TMEscore high correlates with longer survival in OS patients, elevated immune cell infiltration, increased immune checkpoints, and increased sensitivity to chemotherapy."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "TMEscore high correlates with longer survival in OS patients, elevated immune cell infiltration, increased immune checkpoints, and increased sensitivity to chemotherapy.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:36065454"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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After 50 days, all mice were euthanized via CO2 inhalation. Mouse experim", "s Nude mice (male, 4 weeks old) were used as in vivo tumor models. 100 μL of cells transfected wi", "cule to determine the expression of CD4+ TMA in vivo, was detected by RT-PCR in 36 OS samples fro", "EVI2B on OS cells, we performed in vitro and in vivo. Transwell assays revealed that OS cell migr"], "order_basis": "paper_text_order:1986", "id": "assay:2"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.85, "evidence": ["sed as in vivo tumor models. 100 μL of cells transfected with NC or the overexpression of EVI2B (OE-E"], "order_basis": "paper_text_order:2024", "id": "assay:3"}, {"role": "data_generation", "definition_id": "flow_cytometry", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ignificantly suppressed (Figure 9(g)), while flow cytometry showed that OE-EVI2B cell apoptosis levels w", "ects of EVI2B on apoptosis were evaluated by flow cytometry. (i) Images of the subcutaneous tumor."], "order_basis": "paper_text_order:4811", "id": "assay:4"}, {"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["ile flow cytometry showed that OE-EVI2B cell apoptosis levels were increased (Figure 9(h)). The ove", "cell proliferation. (h) Effects of EVI2B on apoptosis were evaluated by flow cytometry. 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