Optimal combination of immune checkpoint and senescence molecule predicts adverse outcomes in patients with acute myeloid leukemia.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37070487", "kind": "science-record", "revision": 3, "content_hash": "sha256:fbbebab0d8af9df73456404dfc2103d9e656c09a5857b87f46decdf9bc1185f1", "created_at": "2026-11-01T19:01:44Z", "updated_at": "2026-11-01T22:09:17Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Optimal combination of immune checkpoint and senescence molecule predicts adverse outcomes in patients with acute myeloid leukemia.", "doi": "10.1080/07853890.2023.2201507", "pmid": "37070487", "authors": ["Peipei Wang", "Yuling Zhang", "Qinghua Cai", "Qingqin Long", "Shiyi Pan", "Wei Zhou", "Tingfen Deng", "Wenjian Mo", "Shunqing Wang", "Yuping Zhang", "Caixia Wang", "Cunte Chen"], "journal": "Annals of medicine", "year": 2023, "abstract": "BACKGROUND: High expression of immune checkpoints (ICs) and senescence molecules (SMs) contributes to T cell dysfunction, tumor escape, and progression, but systematic evaluation of them in co-expression patterns and prognosis in acute myeloid leukemia (AML) was lacking.\nMETHODS: Three publicly available datasets (TCGA, Beat-AML, and GSE71014) were first used to explore the effect of IC and SM combinations on prognosis and the immune microenvironment in AML, and bone marrow samples from 68 AML patients from our clinical center (GZFPH) was further used to validate the findings.\nRESULTS: High expression of CD276, Bcl2-associated athanogene 3 (BAG3), and SRC was associated with poor overall survival (OS) of AML patients. CD276/BAG3/SRC combination, standard European Leukemia Net (ELN) risk stratification, age, and French-American-British (FAB) subtype were used to construct a nomogram model. Interestingly, the new risk stratification derived from the nomogram was better than the standard ELN risk stratification in predicting the prognosis for AML. A weighted combination of CD276 and BAG3/SRC positively corrected with TP53 mutation, p53 pathway, CD8+ T cells, activated memory CD4+ T cells, T-cell senescence score, and Tumor Immune Dysfunction and Exclusion (TIDE) score estimated by T-cell dysfunction.\nCONCLUSION: High expression of ICs and SMs was associated with poor OS of AML patients. The co-expression patterns of CD276 and BAG3/SRC might be potential biomarkers for risk stratification and designing combinational immuno-targeted therapy in AML.Key MessagesHigh expression of CD276, BAG3, and SRC was associated with poor overall survival of AML patients.The co-expression patterns of CD276 and BAG3/SRC might be potential biomarkers for risk stratification and designing combinational immuno-targeted therapy in AML.", "claims": [{"id": "claim-method", "statement": "Multivariate COX regression of these 3 co-expression genes (CD276 and BAG3/SRC) was analyzed, and the following formula can be used to calculate the risk score of each patient according to the coefficients in the TCGA dataset: risk score = 1.12 × (CD276 expression level) + 1.23 × (BAG3 expression level) +1.27 × (SRC expression level) (Figure 5(A,B)).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37070487", "locator": "sections[13] \"Weighted combinations of CD276 and BAG3/SRC associated with clinical outcome\" paragraph 2", "quote": "Multivariate COX regression of these 3 co-expression genes (CD276 and BAG3/SRC) was analyzed, and the following formula can be used to calculate the risk score of each patient according to the coefficients in the TCGA dataset: risk score = 1.12 × (CD276 expression level) + 1.23 × (BAG3 expression level) +1.27 × (SRC expression level) (Figure 5(A,B))."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets used and analyzed in the current study are available from the corresponding author upon reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37070487", "locator": "sections[24] \"Data availability\" paragraph 2", "quote": "The datasets used and analyzed in the current study are available from the corresponding author upon reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "A weighted combination of CD276, BAG3, and SRC stratified AML prognosis and was associated with significantly shorter overall survival in the GZFPH cohort (HR = 4.67; 95% CI: 2.31 to 9.44).", "kind": "quantitative", "target": {"value": 95.0, "unit": "per cent", "tolerance": null, "source": "Patients with high-risk scores had significantly shorter OS than patients with a low-risk score in the TCGA, Beat-AML, and GSE71014 datasets (p < 0.01), which was confirmed in the GZFPH dataset [p < 0.001; hazard ratio (HR) = 4.67; 95% confidence interval (CI): 2.31 to 9.44] (Figure 5(G))."}, "evidence": [{"asset": "source:pmid:37070487", "locator": "sections[13] \"Weighted combinations of CD276 and BAG3/SRC associated with clinical outcome\" paragraph 2", "quote": "Patients with high-risk scores had significantly shorter OS than patients with a low-risk score in the TCGA, Beat-AML, and GSE71014 datasets (p < 0.01), which was confirmed in the GZFPH dataset [p < 0.001; hazard ratio (HR) = 4.67; 95% confidence interval (CI): 2.31 to 9.44] (Figure 5(G))."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "A weighted combination of CD276, BAG3, and SRC stratified AML prognosis and was associated with significantly shorter overall survival in the GZFPH cohort (HR = 4.67; 95% CI: 2.31 to 9.44).", "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:37070487"], "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:GSE71014"], "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:GSE71014"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:37070487", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1080/07853890.2023.2201507", "sha256": 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Schematic diagram of the study design. Transcriptome sequencing data of AML patients in the Cance"], "order_basis": "paper_text_order:3880", "id": "assay:1"}, {"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": ["Multivariate COX regression of these 3 co-expression genes (CD276 and BAG3/SRC) was analyzed, and the following formula can be used to calculate the risk score of each patient according to the coefficients in the TCGA dataset: risk score = 1.12 × (CD276 expression level) + 1.23 × (BAG3 expression level) +1.27 × (SRC expression level) (Figure 5(A,B))."], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}