Construction of an ER stress-related prognostic signature for predicting prognosis and screening the effective anti-tumor drug in osteosarcoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38229155", "kind": "science-record", "revision": 4, "content_hash": "sha256:7692c1a0d98bc35a8b14eb41bec2dae720775e70e56e7bd81bf53b5b9ba54221", "created_at": "2026-11-01T19:20:08Z", "updated_at": "2026-11-01T22:53:27Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Construction of an ER stress-related prognostic signature for predicting prognosis and screening the effective anti-tumor drug in osteosarcoma.", "doi": "10.1186/s12967-023-04794-0", "pmid": "38229155", "authors": ["Weidong Chen", "Yan Liao", "Pengxiao Sun", "Jian Tu", "Yutong Zou", "Ji Fang", "Ziyun Chen", "Hongbo Li", "Junkai Chen", "Yuzhong Peng", "Lili Wen", "Xianbiao Xie"], "journal": "Journal of translational medicine", "year": 2024, "abstract": "BACKGROUND: Osteosarcoma is the most common malignant primary bone tumor in infants and adolescents. The lack of understanding of the molecular mechanisms underlying osteosarcoma progression and metastasis has contributed to a plateau in the development of current therapies. Endoplasmic reticulum (ER) stress has emerged as a significant contributor to the malignant progression of tumors, but its potential regulatory mechanisms in osteosarcoma progression remain unknown.\nMETHODS: In this study, we collected RNA sequencing and clinical data of osteosarcoma from The TCGA, GSE21257, and GSE33382 cohorts. Differentially expressed analysis and the least absolute shrinkage and selection operator regression analysis were conducted to identify prognostic genes and construct an ER stress-related prognostic signature (ERSRPS). Survival analysis and time dependent ROC analysis were performed to evaluate the predictive performance of the constructed prognostic signature. The \"ESTIMATE\" package and ssGSEA algorithm were utilized to evaluate the differences in immune cells infiltration between the groups. Cell-based assays, including CCK-8, colony formation, and transwell assays and co-culture system were performed to assess the effects of the target gene and small molecular drug in osteosarcoma. Animal models were employed to assess the anti-osteosarcoma effects of small molecular drug.\nRESULTS: Five genes (BLC2, MAGEA3, MAP3K5, STC2, TXNDC12) were identified to construct an ERSRPS. The ER stress-related gene Stanniocalcin 2 (STC2) was identified as a risk gene in this signature. Additionally, STC2 knockdown significantly inhibited osteosarcoma cell proliferation, migration, and invasion. Furthermore, the ER stress-related gene STC2 was found to downregulate the expression of MHC-I molecules in osteosarcoma cells, and mediate immune responses through influencing the infiltration and modulating the function of CD8+ T cells. Patients categorized by risk scores showed distinct immune status, and immunotherapy response. ISOX was subsequently identified and validated as an effective anti-osteosarcoma drug through a combination of CMap database screening and in vitro and in vivo experiments.\nCONCLUSION: The ERSRPS may guide personalized treatment decisions for osteosarcoma, and ISOX holds promise for repurposing in osteosarcoma treatment.", "claims": [{"id": "claim-method", "statement": "The prognostic performance of the ERSRPS was assessed using Kaplan–Meier analysis and time-dependent ROC analysis.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38229155", "locator": "sections[5] \"Construction and validation of the endoplasmic reticulum stress-related prognostic signature\" paragraph 2", "quote": "The prognostic performance of the ERSRPS was assessed using Kaplan–Meier analysis and time-dependent ROC analysis."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. These data can be found in: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgiacc=GSE21257,GSE33382,GSE35640,GSE78220 and https://ocg.cancer.gov/programs/target.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38229155", "locator": "sections[38] \"notes\" paragraph 1", "quote": "Publicly available datasets were analyzed in this study. These data can be found in: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgiacc=GSE21257,GSE33382,GSE35640,GSE78220 and https://ocg.cancer.gov/programs/target."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The prognostic model demonstrated high sensitivity and specificity, with an area under the ROC curve (AUC) of 0.81 for 1-year, 0.82 for 3-year, and 0.79 for 5-year survival predictions (Fig. 2E).", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38229155", "locator": "sections[22] \"Construction of a prognostic risk score model for osteosarcoma based on ERSRGs\" paragraph 3", "quote": "The prognostic model demonstrated high sensitivity and specificity, with an area under the ROC curve (AUC) of 0.81 for 1-year, 0.82 for 3-year, and 0.79 for 5-year survival predictions (Fig. 2E)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The prognostic model demonstrated high sensitivity and specificity, with an area under the ROC curve (AUC) of 0.81 for 1-year, 0.82 for 3-year, and 0.79 for 5-year survival predictions (Fig. 2E).", "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:38229155"], "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. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE21257"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE21257"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:38229155", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12967-023-04794-0", "sha256": "sha256:28180d2db02a8c1a55029c04ca08a68fea87764f1e062ffd96b7f74eea853c43", "bytes": 54190, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s12967-023-04794-0", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10792867", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE21257", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE21257", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE21257", "version": null, "note": "Publicly available datasets were analyzed in this study. 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METHODS: In this study, we collected RNA sequencing and clinical data of osteosarcoma from The T"], "order_basis": "paper_text_order:611", "id": "assay:1"}, {"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": ["een the groups. Cell-based assays, including CCK-8, colony formation, and transwell assays and"], "order_basis": "paper_text_order:1236", "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": ["k gene in this signature. Additionally, STC2 knockdown significantly inhibited osteosarcoma cell pr"], "order_basis": "paper_text_order:1711", "id": "assay:3"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["of CMap database screening and in vitro and in vivo experiments. CONCLUSION: The ERSRPS may guid", "ISOX at doses of 50 or 100 mg/kg daily. The mice were monitored every 3 days for 3 weeks. Five mic"], "order_basis": "paper_text_order:2290", "id": "assay:4"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["with 10% fetal bovine serum, while the other cell lines were cultured in high-glucose DMED medium supplemented wit", "-sen University. The cell line hFOB 1.19 was cultured in DMED/F12k medium supplemented with 10% fetal", "ovine serum, while the other cell lines were cultured in high-glucose DMED medium supplemented with 1", "d methods Cell culture Cell lines (hFOB1.19, U2OS, U2R, HOS, MNNG/HOS, 143B, SJSA-1, G292, SAO"], "order_basis": "paper_text_order:2517", "id": "assay:5"}, {"role": "analysis", "definition_id": "diagnostic_evaluation", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["confusion_counts", "roc_curve", "sensitivity_specificity", "solve_confusion_matrix", "classification_metrics", "published_precision_envelope"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["The prognostic performance of the ERSRPS was assessed using Kaplan–Meier analysis and time-dependent ROC analysis."], "order_basis": "consumes_earlier_output", "id": "assay:6"}]}