Identification of STAB1 in Multiple Datasets as a Prognostic Factor for Cytogenetically Normal AML: Mechanism and Drug Indications.

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Nucleic acids", "year": 2019, "abstract": "Cytogenetically normal acute myeloid leukemia (CN-AML) presents with diverse outcomes in different patients and is categorized as an intermediate prognosis group. It is important to identify prognostic factors for CN-AML risk stratification. In this study, using the TCGA CN-AML dataset, we found that the scavenger receptor stabilin-1 (STAB1) is a prognostic factor for poor outcomes and validated it in three other independent CN-AML datasets. The high STAB1 expression (STAB1high) group had shorter event-free survival compared with the low STAB1 expression (STAB1low) group in both the TCGA dataset (n = 79; p = 0.0478) and GEO: GSE6891 dataset (n = 187; p = 0.0354). Differential expression analysis between the STAB1high and STAB1low groups revealed that upregulated genes in the STAB1high group were enriched in pathways related to cell adhesion and migration and immune responses. We confirmed that STAB1 suppression inhibits cell growth in KG1a and NB4 leukemia cells. Expression correlation analyses between STAB1 and cancer drug targets suggested that patients in the STAB1low group are more sensitive to the BCL2 inhibitor venetoclax, and we confirmed it in cell lines. In conclusion, we identified STAB1 as a prognostic factor for CN-AML in multiple datasets, explored its underlying mechanism, and provided potential therapeutic indications.", "claims": [{"id": "claim-method", "statement": "For multivariate analyses, the multivariable Cox proportional hazards model was used to assess the association between STAB1 expression and OS or EFS in the presence of other known clinical factors such as age, sex, WBC counts, mutation status, and FAB classification.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31670197", "locator": "sections[12] \"Survival Analysis\" paragraph 2", "quote": "For multivariate analyses, the multivariable Cox proportional hazards model was used to assess the association between STAB1 expression and OS or EFS in the presence of other known clinical factors such as age, sex, WBC counts, mutation status, and FAB classification."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": null, "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:31670197"], "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": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. 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We also obtained four CN-AML microarray datasets: GSE12417 test dataset (GSE12417A;"], "order_basis": "paper_text_order:2958", "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": ["n = 47) and >2 years (n = 32). Cell Culture, Transfection with siRNA, and RNA Expression Quantificatio", "e containing 5% CO2 and 95% air at 37°C. For transfection, the cultured cell lines were seeded in six-", "ell lines were seeded in six-well plates and transfected with 100 nmol/L STAB1 siRNAs or control olig", "TGGTCACTTGTA-3′, respectively. 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