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pmid:35789548

Establishment of a risk model by integrating hypoxia genes in predicting prognosis of esophageal squamous cell carcinoma.

Wanyi Xiao · Peng Tang · Zhilin Sui · Youming Han · Gang Zhao · Xianxian Wu · Yueyang Yang · Ningning Zhu · Lei Gong · Zhentao Yu · Hongdian Zhang

Cancer medicine · 2023 doi:10.1002/cam4.5002

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Experiment

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Data

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title
Establishment of a risk model by integrating hypoxia genes in predicting prognosis of esophageal squamous cell carcinoma.
doi
10.1002/cam4.5002
pmid
35789548
authors array · 11 items
[0]
Wanyi Xiao
[1]
Peng Tang
[2]
Zhilin Sui
[3]
Youming Han
[4]
Gang Zhao
[5]
Xianxian Wu
[6]
Yueyang Yang
[7]
Ningning Zhu
[8]
Lei Gong
[9]
Zhentao Yu
[10]
Hongdian Zhang
journal
Cancer medicine
year
2023
abstract
BACKGROUND: Esophageal squamous cell carcinoma (ESCC) has a dismal prognosis, and hypoxia plays a key role in metastasis and proliferation of ESCC. Thus, we aimed to develop a hypoxia-based gene signature to assist in the treatment decisions and prognosis. METHODS: We performed consensus clustering analysis on samples from GSE53625 dataset from the Gene Expression Omnibus (GEO) database and used weighted gene co-expression network analysis to filter out candidate modules, which were then intersected with differentially expressed genes from clustered subgroups to obtain hypoxia-related genes (HRGs). After that, the aforementioned genes were used to construct risk score models and validated in The Cancer Genome Atlas (TCGA) database and Cox regression analysis were used to construct a nomogram. Immunohistochemical was used to detect protein expression levels of relevant genes. Moreover, the relationship between risk scores and tumor microenvironment was explored. RESULTS: A hypoxia risk model containing six genes (PNPLA1, CARD18, IL-18, SLC37A2, ADAMTS18, and FAM83C) was constructed by screening key HRGs. Poorer prognosis in the high-risk group than in the low-risk group. And Cox regression analysis showed that risk score was an independent prognostic factor. The nomogram based on risk scores could well predict 1-, 3-, and 5-year survival. P53, Wnt, and hypoxia signaling pathways may be some regulatory mechanisms of hypoxia associated with the tumor microenvironment. In addition, we confirmed the high expression of BGN and low expression of IL-18 in ESCC tissues. CONCLUSIONS: Our study determined the prognostic value of a 6-hypoxia gene signature and a prognostic model, providing potential prognostic predictors and therapeutic targets for ESCC.
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The stepAIC algorithm running in the R “MASS” package was used to construct an optimal prognostic model, based on the combination of expression profiles that intersected from selected modules and DEGs and prognostic information from 179 ESCC samples.
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The stepAIC algorithm running in the R “MASS” package was used to construct an optimal prognostic model, based on the combination of expression profiles that intersected from selected modules and DEGs and prognostic information from 179 ESCC samples.
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A six-gene hypoxia risk model was constructed and showed poorer prognosis in the high-risk group, with independent prognostic value and nomograms capable of predicting 1-, 3-, and 5-year survival.
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A hypoxia risk model containing six genes (PNPLA1, CARD18, IL‐18, SLC37A2, ADAMTS18, and FAM83C) was constructed by screening key HRGs. Poorer prognosis in the high‐risk group than in the low‐risk group. And Cox regression analysis showed that risk score was an independent prognostic factor. The nomogram based on risk scores could well predict 1‐, 3‐, and 5‐year survival.
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A six-gene hypoxia risk model was constructed and showed poorer prognosis in the high-risk group, with independent prognostic value and nomograms capable of predicting 1-, 3-, and 5-year survival.
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Deidentified data and related documents will be made available upon request.
basis
The paper names GSE53625 in Gene Expression Omnibus and the accession resolves in the repository. No dataset was downloaded and no licence was read.
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35789548", "kind": "science-record", "revision": 4, "content_hash": "sha256:171c74dd1f2531d3996542dc1c7d932f953c0b1dc94fb15c438fd5e45039ccfe", "created_at": "2026-11-01T18:14:49Z", "updated_at": "2026-11-01T22:06:56Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Establishment of a risk model by integrating hypoxia genes in predicting prognosis of esophageal squamous cell carcinoma.", "doi": "10.1002/cam4.5002", "pmid": "35789548", "authors": ["Wanyi Xiao", "Peng Tang", "Zhilin Sui", "Youming Han", "Gang Zhao", "Xianxian Wu", "Yueyang Yang", "Ningning Zhu", "Lei Gong", "Zhentao Yu", "Hongdian Zhang"], "journal": "Cancer medicine", "year": 2023, "abstract": "BACKGROUND: Esophageal squamous cell carcinoma (ESCC) has a dismal prognosis, and hypoxia plays a key role in metastasis and proliferation of ESCC. Thus, we aimed to develop a hypoxia-based gene signature to assist in the treatment decisions and prognosis.\nMETHODS: We performed consensus clustering analysis on samples from GSE53625 dataset from the Gene Expression Omnibus (GEO) database and used weighted gene co-expression network analysis to filter out candidate modules, which were then intersected with differentially expressed genes from clustered subgroups to obtain hypoxia-related genes (HRGs). After that, the aforementioned genes were used to construct risk score models and validated in The Cancer Genome Atlas (TCGA) database and Cox regression analysis were used to construct a nomogram. Immunohistochemical was used to detect protein expression levels of relevant genes. Moreover, the relationship between risk scores and tumor microenvironment was explored.\nRESULTS: A hypoxia risk model containing six genes (PNPLA1, CARD18, IL-18, SLC37A2, ADAMTS18, and FAM83C) was constructed by screening key HRGs. Poorer prognosis in the high-risk group than in the low-risk group. And Cox regression analysis showed that risk score was an independent prognostic factor. The nomogram based on risk scores could well predict 1-, 3-, and 5-year survival. P53, Wnt, and hypoxia signaling pathways may be some regulatory mechanisms of hypoxia associated with the tumor microenvironment. In addition, we confirmed the high expression of BGN and low expression of IL-18 in ESCC tissues.\nCONCLUSIONS: Our study determined the prognostic value of a 6-hypoxia gene signature and a prognostic model, providing potential prognostic predictors and therapeutic targets for ESCC.", "claims": [{"id": "claim-method", "statement": "The stepAIC algorithm running in the R “MASS” package was used to construct an optimal prognostic model, based on the combination of expression profiles that intersected from selected modules and DEGs and prognostic information from 179 ESCC samples.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35789548", "locator": "sections[8] \"Construction and evaluation of the prognosis prediction model\" paragraph 2", "quote": "The stepAIC algorithm running in the R “MASS” package was used to construct an optimal prognostic model, based on the combination of expression profiles that intersected from selected modules and DEGs and prognostic information from 179 ESCC samples."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Deidentified data and related documents will be made available upon request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35789548", "locator": "sections[30] \"DATA AVAILABILITY STATEMENT\" paragraph 2", "quote": "Deidentified data and related documents will be made available upon request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "A six-gene hypoxia risk model was constructed and showed poorer prognosis in the high-risk group, with independent prognostic value and nomograms capable of predicting 1-, 3-, and 5-year survival.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35789548", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "A hypoxia risk model containing six genes (PNPLA1, CARD18, IL‐18, SLC37A2, ADAMTS18, and FAM83C) was constructed by screening key HRGs. Poorer prognosis in the high‐risk group than in the low‐risk group. And Cox regression analysis showed that risk score was an independent prognostic factor. The nomogram based on risk scores could well predict 1‐, 3‐, and 5‐year survival."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "A six-gene hypoxia risk model was constructed and showed poorer prognosis in the high-risk group, with independent prognostic value and nomograms capable of predicting 1-, 3-, and 5-year survival.", "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:35789548"], "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:GSE53625"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "blocked", "blocked_on": "method:group_comparison_wilcoxon", "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:GSE53625"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:group_comparison_wilcoxon"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:35789548", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": 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