HIVEP3 cooperates with ferroptosis gene signatures to confer adverse prognosis in acute myeloid leukemia.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35535739", "kind": "science-record", "revision": 4, "content_hash": "sha256:759c17ed5f55103c511a9c57a6b8788a3712213e90735d900e59f9e1608b8f73", "created_at": "2026-11-01T18:14:26Z", "updated_at": "2026-11-01T22:06:29Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "HIVEP3 cooperates with ferroptosis gene signatures to confer adverse prognosis in acute myeloid leukemia.", "doi": "10.1002/cam4.4806", "pmid": "35535739", "authors": ["Xiaoning Zhang", "Xiaoyu Zhang", "Kuo Liu", "Wenwen Li", "Jiazheng Wang", "Peng Liu", "Wanshan Ma"], "journal": "Cancer medicine", "year": 2022, "abstract": "BACKGROUND: The human immunodeficiency virus type I enhancer binding protein (HIVEP) family, which contains zinc finger and acid-rich (ZAS) domains, has been demonstrated to be implicated in vital biological processes, such as cell survival, tumor necrosis factor (TNF) signaling, and tumor formation. However, its expression patterns, prognostic relevance, and functional implications in acute myeloid leukemia (AML) remain elusive.\nMETHODS: We inspected HIVEP mRNA expression levels in datasets from The Cancer Genome Atlas (TCGA) and GSE24006. Survival analyses were orchestrated using the web-based bioinformatics platforms and R studio in two AML cohorts. Prognostic value and capacity were assessed by Cox regression analyses. Association of HIVEP3 expression levels with clinical characteristics were analyzed with R and UALCAN. Subsequentially, functional enrichment analyses were operated to interpret HIVEP3 co-expressed gene clusters. A prognostic gene signature was created by the least absolute shrinkage and selection operator (LASSO) regression algorithm. Moreover, bone marrow aspirate smears of AML patients were stained for HIVEP3 by immunohistochemistry (IHC). HIVEP3 expression was examined by qRT-PCR in leukemia cell lines treated with ferroptosis compounds in vitro.\nRESULTS: Augmented transcriptional levels of HIVEP2 and 3 were noted in AML patients (p<0.001). HIVEP3 not only could confer adverse prognosis independently in AML patients, but also was associated with AML subtypes, age, cytogenetic risk, and disease-related molecules. Co-expressed gene clusters of HIVEP3 were enriched in functional pathways related to AML leukemogenesis, such as ribosome, metabolism, and calcium signaling. Combined with multiple tumorigenesis signaling pathways, we proposed an integrated LASSO model with HIVEP3 and ferroptosis regulators AIFM2 and LPCAT3, to predict the outcome for AML patients. Furthernore, altered HIVEP3 expression at the mRNA or protein level was confirmed in sorted leukemia cells and blast cells in bone marrow tissues. In vitro experiments authenticated the involvement of HIVEP3 in ferroptosis signaling pathways.\nCONCLUSIONS: Our findings suggest that HIVEP3 is a de novo independent prognostic indicator, and the crosstalk between HIVEP3 and ferroptosis signaling pathways may inspire a specific perspective on the oncological network of AML.", "claims": [{"id": "claim-method", "statement": "As previously reported, univariate and multivariate Cox regression analyses were employed to screen for the potential prognostic indicators in the TCGA‐LAML cohort (n = 151).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35535739", "locator": "sections[5] \"Univariate and multivariate Cox regression analyses\" paragraph 2", "quote": "As previously reported, univariate and multivariate Cox regression analyses were employed to screen for the potential prognostic indicators in the TCGA‐LAML cohort (n = 151)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets analyzed for this study can be found in the National Cancer Institute (NCI) TCGA cancers (TCGA‐LAML) https://portal.gdc.cancer.gov/, GTEx (normal tissues) https://gtexportal.org/home/datasets, and Gene Expression Omnibus (GEO: GSE12417, GSE24006) https://www.ncbi.nlm.nih.gov/geo. All data that support the findings of this study are available from the corresponding author upon reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35535739", "locator": "sections[27] \"DATA AVAILABILITY STATEMENT\" paragraph 2", "quote": "The datasets analyzed for this study can be found in the National Cancer Institute (NCI) TCGA cancers (TCGA‐LAML) https://portal.gdc.cancer.gov/, GTEx (normal tissues) https://gtexportal.org/home/datasets, and Gene Expression Omnibus (GEO: GSE12417, GSE24006) https://www.ncbi.nlm.nih.gov/geo. All data that support the findings of this study are available from the corresponding author upon reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Elevated HIVEP3 expression independently predicts adverse overall survival in AML patients (HR = 1.4; 95% CI, 1.07–1.7; p = 0.011).", "kind": "quantitative", "target": {"value": 95.0, "unit": "per cent", "tolerance": null, "source": "The forest plots represented the prognostic significance of augmented HIVEP3 expression for dismal outcomes of AML patients (HR = 1.4; 95% (CI), 1.07–1.7; p = 0.011), independent of age, poor cytogenetic risk, and specific gene mutations (Figure 3A and Figure S1)."}, "evidence": [{"asset": "source:pmid:35535739", "locator": "sections[13] \"Prognostic implications of HIVEP2 and 3 in AML\" paragraph 6", "quote": "The forest plots represented the prognostic significance of augmented HIVEP3 expression for dismal outcomes of AML patients (HR = 1.4; 95% (CI), 1.07–1.7; p = 0.011), independent of age, poor cytogenetic risk, and specific gene mutations (Figure 3A and Figure S1)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Elevated HIVEP3 expression independently predicts adverse overall survival in AML patients (HR = 1.4; 95% CI, 1.07–1.7; p = 0.011).", "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:35535739"], "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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