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pmid:34217310

Constructe a novel 5 hypoxia genes signature for cervical cancer.

Yang Yang · Yaling Li · Ruiqun Qi · Lan Zhang

Cancer cell international · 2021 doi:10.1186/s12935-021-02050-3

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complete

Experiment

complete

Data

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Analysis

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title
Constructe a novel 5 hypoxia genes signature for cervical cancer.
doi
10.1186/s12935-021-02050-3
pmid
34217310
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[0]
Yang Yang
[1]
Yaling Li
[2]
Ruiqun Qi
[3]
Lan Zhang
journal
Cancer cell international
year
2021
abstract
BACKGROUND: Hypoxia, which affects the development, metastasis and prognosis of cancer, represents a key feature of cancer. This study describe a hypoxia risk factor model, with predicting the prognosis of cervical cancer. METHODS: Based on hypoxia pathway related genes, we divided cervical cancer samples into high and low expression groups. A cox analysis was then performed. Genes from these cervical cancer samples showing a significant impact on OS were selected for cluster analysis to obtain two subtypes. The TPM dataset of TCGA was divided into training and validation sets. For the training set, a lasso analysis was conducted as based on cox analysis of meaningful genes and a risk factor model was constructed. The constructed model was verified in internal and external data sets. Finally, RT-PCR, immunohistochemistry were used to detect the expression of relative genes or proteins and functional assays were used to evaluate the biological function of signature genes. RESULTS: Two molecular subtypes were obtained, Cluster2 vs Cluster1.These subtypes were obtained by clustering with a total of 149 DEGs (Differential expressed genes) being in line with this standard, of which 27 were up-regulated and 122 were down-regulated. The five genes with lambda = 0.0571 were selected to construct the model, the RiskScore = AK4*0.042 + HK2*0.021 + P4HA1*0.22 + TGFBI*0.1 + VEGFA*0.077. Further, in order to verify the signature, we used TCGA-test and GSE44001 chip datasets to test, and finally got a good risk prediction effect in those datasets. Moreover, the result of RT-PCR and immunohistochemistry demonstrated that AK4, HK2, P4HA1, TGFBI and VEGFA were all highly expressed in these cervical cancer tissue samples. The functional study shown that expression of AK4, HK2, P4HA1, TGFBI and VEGFA can regulate the proliferation, migration, and invasion ability of cervical cancer cells in vitro. CONCLUSIONS: In summary, we developed a 5-gene signature prognostic hierarchical system based on the hypoxic pathway of cervical cancer, which is independent of clinical characteristics. And also conducted experimental verifications on these signature gene. Therefore, we propose that use of this classifier as a molecular diagnostic test can provide an effective means for evaluating the prognostic risk of cervical cancer patients, and provide potential targets for the treatment of cervical cancer patients.
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A cox analysis, as based on overall survival (OS), was performed and genes with a p < 0.05 were screened.
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sections[4] "Cluster analysis of TCGA cervical cancer" paragraph 2
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A cox analysis, as based on overall survival (OS), was performed and genes with a p < 0.05 were screened.
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The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
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evidence object · 3 fields
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0.8
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null
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A cox analysis, as based on overall survival (OS), was performed and genes with a p < 0.05 were screened.
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method.reader_named_unmapped
capability object · 3 fields
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candidate
Automated Assays Laravel application and simulated adapters
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The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here.
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GSE44001
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The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
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The paper names GSE44001 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read.
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nal and external data sets. Finally, RT-PCR, immunohistochemistry were used to detect the expression of relati
[1]
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34217310", "kind": "science-record", "revision": 7, "content_hash": "sha256:6f68fdf3816d0489e8542e7f0c377da33fc3afeb1b5afcbe748f88fa4c3e9256", "created_at": "2026-11-01T15:41:41Z", "updated_at": "2026-11-01T22:04:06Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Constructe a novel 5 hypoxia genes signature for cervical cancer.", "doi": "10.1186/s12935-021-02050-3", "pmid": "34217310", "authors": ["Yang Yang", "Yaling Li", "Ruiqun Qi", "Lan Zhang"], "journal": "Cancer cell international", "year": 2021, "abstract": "BACKGROUND: Hypoxia, which affects the development, metastasis and prognosis of cancer, represents a key feature of cancer. This study describe a hypoxia risk factor model, with predicting the prognosis of cervical cancer.\nMETHODS: Based on hypoxia pathway related genes, we divided cervical cancer samples into high and low expression groups. A cox analysis was then performed. Genes from these cervical cancer samples showing a significant impact on OS were selected for cluster analysis to obtain two subtypes. The TPM dataset of TCGA was divided into training and validation sets. For the training set, a lasso analysis was conducted as based on cox analysis of meaningful genes and a risk factor model was constructed. The constructed model was verified in internal and external data sets. Finally, RT-PCR, immunohistochemistry were used to detect the expression of relative genes or proteins and functional assays were used to evaluate the biological function of signature genes.\nRESULTS: Two molecular subtypes were obtained, Cluster2 vs Cluster1.These subtypes were obtained by clustering with a total of 149 DEGs (Differential expressed genes) being in line with this standard, of which 27 were up-regulated and 122 were down-regulated. The five genes with lambda = 0.0571 were selected to construct the model, the RiskScore = AK4*0.042 + HK2*0.021 + P4HA1*0.22 + TGFBI*0.1 + VEGFA*0.077. Further, in order to verify the signature, we used TCGA-test and GSE44001 chip datasets to test, and finally got a good risk prediction effect in those datasets. Moreover, the result of RT-PCR and immunohistochemistry demonstrated that AK4, HK2, P4HA1, TGFBI and VEGFA were all highly expressed in these cervical cancer tissue samples. The functional study shown that expression of AK4, HK2, P4HA1, TGFBI and VEGFA can regulate the proliferation, migration, and invasion ability of cervical cancer cells in vitro.\nCONCLUSIONS: In summary, we developed a 5-gene signature prognostic hierarchical system based on the hypoxic pathway of cervical cancer, which is independent of clinical characteristics. And also conducted experimental verifications on these signature gene. Therefore, we propose that use of this classifier as a molecular diagnostic test can provide an effective means for evaluating the prognostic risk of cervical cancer patients, and provide potential targets for the treatment of cervical cancer patients.", "claims": [{"id": "claim-method", "statement": "A cox analysis, as based on overall survival (OS), was performed and genes with a p < 0.05 were screened.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34217310", "locator": "sections[4] \"Cluster analysis of TCGA cervical cancer\" paragraph 2", "quote": "A cox analysis, as based on overall survival (OS), was performed and genes with a p < 0.05 were screened."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34217310", "locator": "sections[40] \"notes\" paragraph 1", "quote": "The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "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:34217310"], "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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