ArticleMolecular therapy oncolytics2019
Hypoxia-Induced Upregulation of HE4 Is Responsible for Resistance to Radiation Therapy of Gastric Cancer.
Article in Molecular therapy oncolytics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 24 citations in OpenAlex.
- HE4 as a Prognostic Biomarker of Major Adverse Cardiovascular Events in Patients with Abdominal Aortic Aneurysm: A Canadian Prospective Observational Study.Biomedicines · 2025Article
- Elevated plasma levels of WAP four-disulfide core domain 2 as a potential prognostic biomarker for various cancers.Frontiers in oncology · 2025Article
- Article
- Recent Insight about HE4 Role in Ovarian Cancer Oncogenesis.International journal of molecular sciences · 2023Review
- HIF1α/CCL7/KIAA1199 axis mediates hypoxia-induced gastric cancer aggravation and glycolysis alteration.Journal of clinical biochemistry and nutrition · 2023Article
- A bioinformatic analysis of WFDC2 (HE4) expression in high grade serous ovarian cancer reveals tumor-specific changes in metabolic and extracellular matrix gene expression.Medical oncology (Northwood, London, England) · 2022Article
- Hypoxia-Induced Cancer Cell Responses Driving Radioresistance of Hypoxic Tumors: Approaches to Targeting and Radiosensitizing.Cancers · 2021Review
- The biomarker HE4 (WFDC2) promotes a pro-angiogenic and immunosuppressive tumor microenvironment via regulation of STAT3 target genes.Scientific reports · 2020Article
- CircHIPK3 Promotes Metastasis of Gastric Cancer via miR-653-5p/miR-338-3p-NRP1 Axis Under a Long-Term Hypoxic Microenvironment.Frontiers in oncology · 2020Article
- Deficiency of 15-LOX-1 Induces Radioresistance through Downregulation of MacroH2A2 in Colorectal Cancer.Cancers · 2019Article
- Diagnostic value of human epididymis protein 4 in malignant pleural effusion in lung cancer.Cancer biomarkers : section A of Disease markers · 2019Article
- Value of human epididymis secretory protein 4 in differentiating malignant from benign pleural effusion: an analysis of two cohorts.Therapeutic advances in respiratory diseaseArticle
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Upregulation of human epididymis protein 4 (HE4) is often observed in different types of cancers, including gastric cancer (GC), but the association of elevated HE4 level with radiation resistance in GC remains unclear. The expression of HE4 and hypoxia-inducible factor 1α subunit (HIF1α) was assessed in GC patient samples and cell lines. Chromatin immunoprecipitation (ChIP) and luciferase reporter assays were performed to reveal the regulation between HE4 and HIF1α. Stable HE4 knockdown and HIF1α overexpression were introduced into GC cell lines to study the role of HE4 in the resistance of GC to radiation therapy. Colony formation assay and the xenograft mouse model were used to investigate the effects of radiation on GC cells. HE4 and HIF1α were upregulated in both GC patient tissues and GC cells. Hypoxia and HIF1α upregulated HE4 by directly targeting the hypoxia response element in its promoter region. Stable HE4 knockdown significantly sensitized GC cells and xenograft tumors to radiation. HIF1α overexpression markedly elevated the radiation resistance of GC cells, which was almost completely abolished by HE4 knockdown. Hypoxia-induced upregulation of HE4 is responsible for resistance to radiation therapy of GC, suggesting that HE4 knockdown or inhibition, combined with radiation therapy, holds great potential in the clinical treatment of GC.
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