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pmid:35023280

Ferroptosis-related gene NOX4, CHAC1 and HIF1A are valid biomarkers for stomach adenocarcinoma.

Ruoxi Xiao · Shasha Wang · Jing Guo · Shihai Liu · Aiping Ding · Gongjun Wang · Wenqian Li · Yuqi Zhang · Xiaoqian Bian · Shufen Zhao · Wensheng Qiu

Journal of cellular and molecular medicine · 2022 doi:10.1111/jcmm.17171

Paper

complete

Experiment

complete

Data

partial

Analysis

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Execution

absent

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pmid:35023280
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title
Ferroptosis-related gene NOX4, CHAC1 and HIF1A are valid biomarkers for stomach adenocarcinoma.
doi
10.1111/jcmm.17171
pmid
35023280
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[0]
Ruoxi Xiao
[1]
Shasha Wang
[2]
Jing Guo
[3]
Shihai Liu
[4]
Aiping Ding
[5]
Gongjun Wang
[6]
Wenqian Li
[7]
Yuqi Zhang
[8]
Xiaoqian Bian
[9]
Shufen Zhao
[10]
Wensheng Qiu
journal
Journal of cellular and molecular medicine
year
2022
abstract
Ferroptosis is a regulated cell death nexus linking metabolism, redox biology and diseases including cancer. The aim of the present study was to identify a ferroptosis-related gene prognostic signature for stomach adenocarcinoma (STAD) by systematic analysis of transcriptional profiles from The Cancer Genome Atlas (TCGA), GEO and a clinical cohort from our centre. We developed a predictive model based on three ferroptosis-related genes (CHAC1, NOX4 and HIF1A), gene expression data and corresponding clinical outcomes were obtained from the TCGA database, and the reliability of this model was verified with GSE15459 and 51 queues in our centre. ROC curve showed better predictive ability using the risk score. Immune cell enrichment analysis demonstrated that the types of immune cells and their expression levels in the high-risk group were significantly different from those in the low-risk group. The experimental results confirmed that NOX4 was upregulated and CHAC1 was downregulated in the STAD tissues compared with the normal stomach mucosal tissues (p < 0.05). In sum, the ferroptosis-related gene signature can accurately predict the outcomes of patients with STAD, providing valuable insights for personalized treatment. As the signature also has relevance to the immune characteristics, it may help improve the efficacy of personalized immunotherapy.
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Kaplan‐Meier survival analysis and time‐dependent ROC curve analysis were applied to evaluate the prognostic capability of the signature.
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sections[6] "Construction and verification of the ferroptosis‐related prognostic model" paragraph 5
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Kaplan‐Meier survival analysis and time‐dependent ROC curve analysis were applied to evaluate the prognostic capability of the signature.
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The data that support the findings of this study are available from the corresponding author upon reasonable request.
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The three-gene ferroptosis risk score predicted overall survival in STAD, with TCGA AUCs of 0.67, 0.70, and 0.75 at 1, 3, and 5 years, respectively, and significant survival differences in both validation cohorts.
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The Kaplan‐Meier survival curves of the two test cohorts both showed that the survival probability in the high‐risk group was significantly shorter than that in the low‐risk group (p < 0.0001).
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sections[12] "Establishment and verification of a ferroptosis‐related prognostic model in STAD" paragraph 4
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The area under the curve (AUCs) for 1, 3 and 5 years was 0.67, 0.7 and 0.75 respectively (Figure 3A).
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sections[12] "Establishment and verification of a ferroptosis‐related prognostic model in STAD" paragraph 5
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The Kaplan‐Meier survival curves of the two test cohorts both showed that the survival probability in the high‐risk group was significantly shorter than that in the low‐risk group (p < 0.0001).
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The three-gene ferroptosis risk score predicted overall survival in STAD, with TCGA AUCs of 0.67, 0.70, and 0.75 at 1, 3, and 5 years, respectively, and significant survival differences in both validation cohorts.
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35023280", "kind": "science-record", "revision": 5, "content_hash": "sha256:5631485b8a41ac7cf5922589c28b5e02088307ff6eeb43e1c4627ff373788362", "created_at": "2026-11-01T17:36:44Z", "updated_at": "2026-11-01T22:48:13Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Ferroptosis-related gene NOX4, CHAC1 and HIF1A are valid biomarkers for stomach adenocarcinoma.", "doi": "10.1111/jcmm.17171", "pmid": "35023280", "authors": ["Ruoxi Xiao", "Shasha Wang", "Jing Guo", "Shihai Liu", "Aiping Ding", "Gongjun Wang", "Wenqian Li", "Yuqi Zhang", "Xiaoqian Bian", "Shufen Zhao", "Wensheng Qiu"], "journal": "Journal of cellular and molecular medicine", "year": 2022, "abstract": "Ferroptosis is a regulated cell death nexus linking metabolism, redox biology and diseases including cancer. The aim of the present study was to identify a ferroptosis-related gene prognostic signature for stomach adenocarcinoma (STAD) by systematic analysis of transcriptional profiles from The Cancer Genome Atlas (TCGA), GEO and a clinical cohort from our centre. We developed a predictive model based on three ferroptosis-related genes (CHAC1, NOX4 and HIF1A), gene expression data and corresponding clinical outcomes were obtained from the TCGA database, and the reliability of this model was verified with GSE15459 and 51 queues in our centre. ROC curve showed better predictive ability using the risk score. Immune cell enrichment analysis demonstrated that the types of immune cells and their expression levels in the high-risk group were significantly different from those in the low-risk group. The experimental results confirmed that NOX4 was upregulated and CHAC1 was downregulated in the STAD tissues compared with the normal stomach mucosal tissues (p < 0.05). In sum, the ferroptosis-related gene signature can accurately predict the outcomes of patients with STAD, providing valuable insights for personalized treatment. As the signature also has relevance to the immune characteristics, it may help improve the efficacy of personalized immunotherapy.", "claims": [{"id": "claim-method", "statement": "Kaplan‐Meier survival analysis and time‐dependent ROC curve analysis were applied to evaluate the prognostic capability of the signature.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35023280", "locator": "sections[6] \"Construction and verification of the ferroptosis‐related prognostic model\" paragraph 5", "quote": "Kaplan‐Meier survival analysis and time‐dependent ROC curve analysis were applied to evaluate the prognostic capability of the signature."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The 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:35023280", "locator": "sections[25] \"DATA AVAILABILITY STATEMENT\" paragraph 2", "quote": "The data that support the findings of this study are available from the corresponding author upon reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The three-gene ferroptosis risk score predicted overall survival in STAD, with TCGA AUCs of 0.67, 0.70, and 0.75 at 1, 3, and 5 years, respectively, and significant survival differences in both validation cohorts.", "kind": "quantitative", "target": {"value": 0.0001, "unit": "p-value", "tolerance": null, "source": "The Kaplan‐Meier survival curves of the two test cohorts both showed that the survival probability in the high‐risk group was significantly shorter than that in the low‐risk group (p < 0.0001)."}, "evidence": [{"asset": "source:pmid:35023280", "locator": "sections[12] \"Establishment and verification of a ferroptosis‐related prognostic model in STAD\" paragraph 4", "quote": "The area under the curve (AUCs) for 1, 3 and 5 years was 0.67, 0.7 and 0.75 respectively (Figure 3A)."}, {"asset": "source:pmid:35023280", "locator": "sections[12] \"Establishment and verification of a ferroptosis‐related prognostic model in STAD\" paragraph 5", "quote": "The Kaplan‐Meier survival curves of the two test cohorts both showed that the survival probability in the high‐risk group was significantly shorter than that in the low‐risk group (p < 0.0001)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The three-gene ferroptosis risk score predicted overall survival in STAD, with TCGA AUCs of 0.67, 0.70, and 0.75 at 1, 3, and 5 years, respectively, and significant survival differences in both validation cohorts.", "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:35023280"], "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:GSE15459"], "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:GSE15459"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:35023280", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1111/jcmm.17171", "sha256": "sha256:9c8ecfd3091259e8edd9a7cdf9c72ceb0f1024ffacf79b08e2347d0eab85df08", "bytes": 32552, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1111/jcmm.17171", "version": null, "note": "Full article fetched from PMC; 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