ArticleScientific reports2020
The biomarker HE4 (WFDC2) promotes a pro-angiogenic and immunosuppressive tumor microenvironment via regulation of STAT3 target genes.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 35 citations in OpenAlex.
- Serum human epididymis protein 4 and long-term mortality in U.S. women: a nationally representative cohort study.Clinics (Sao Paulo, Brazil) · 2026Article
- SemanticST: A Scalable Multi-Contextual Graph Learning Framework for Uncovering Spatial Niches and Robust Multi-Sample Integration in Spatial Transcriptomics.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Plasma Proteomics Identifies Proteins and Pathways Associated with Cataract: A Prospective Cohort Study.Ophthalmology science · 2026Article
- Integrated multi-omics analysis: exploring the molecular regulatory mechanisms of HIV infection and identifying the key gene WFDC2.Clinical and experimental medicine · 2026Article
- Systematic profiling of cancer-fibroblast interactions reveals drug combinations in ovarian cancer.Molecular oncology · 2025Article
- Article
- Human epididymis protein 4-annexin II binding promotes aberrant epithelial-fibroblast crosstalk in pulmonary fibrosis.Communications biology · 2025Article
- Human epididymis protein 4, a novel potential biomarker for diagnostic and prognosis monitoring of lung cancer.The clinical respiratory journal · 2024Article
- HE4-based nomogram for predicting overall survival in patients with idiopathic pulmonary fibrosis: construction and validation.European journal of medical research · 2024Article
- Single-cell transcriptomics reveal metastatic CLDN4+ cancer cells underlying the recurrence of malignant pleural effusion in patients with advanced non-small-cell lung cancer.Clinical and translational medicine · 2024Article
- Article
- Recent Insight about HE4 Role in Ovarian Cancer Oncogenesis.International journal of molecular sciences · 2023Review
- Computational identification of novel signature of T2DM-induced nephropathy and therapeutic bioactive compounds fromAmerican journal of translational research · 2023Article
- Novel plasma protein biomarkers from critically ill sepsis patients.Clinical proteomics · 2022Article
- 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
- Human epididymis protein 4 aggravates airway inflammation and remodeling in chronic obstructive pulmonary disease.Respiratory research · 2022Article
- Anti-inflammatory effects of lavender and eucalyptus essential oils on the in vitro cell culture model of bladder pain syndrome using T24 cells.BMC complementary medicine and therapies · 2022Article
- Plasma proteins, cognitive decline, and 20-year risk of dementia in the Whitehall II and Atherosclerosis Risk in Communities studies.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2022Article
- Cell Trajectory-Related Genes of Lung Adenocarcinoma Predict Tumor Immune Microenvironment and Prognosis of Patients.Frontiers in oncology · 2022Article
- The Prognostic Value of Integrated Analysis of Inflammation and Hypoxia-Related Genes in Idiopathic Pulmonary Fibrosis.Frontiers in immunology · 2022Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 1 country.
Funding
Abstract
Epithelial ovarian cancer (EOC) is a highly lethal gynecologic malignancy arising from the fallopian tubes that has a high rate of chemoresistant recurrence and low five-year survival rate. The ovarian cancer biomarker HE4 is known to promote proliferation, metastasis, chemoresistance, and suppression of cytotoxic lymphocytes. In this study, we sought to examine the effects of HE4 on signaling within diverse cell types that compose the tumor microenvironment. HE4 was found to activate STAT3 signaling and promote upregulation of the pro-angiogenic STAT3 target genes IL8 and HIF1A in immune cells, ovarian cancer cells, and endothelial cells. Moreover, HE4 promoted increases in tube formation in an in vitro model of angiogenesis, which was also dependent upon STAT3 signaling. Clinically, HE4 and IL8 levels positively correlated in ovarian cancer patient tissue. Furthermore, HE4 serum levels correlated with microvascular density in EOC tissue and inversely correlated with cytotoxic T cell infiltration, suggesting that HE4 may cause deregulated blood vessel formation and suppress proper T cell trafficking in tumors. Collectively, this study shows for the first time that HE4 has the ability to affect signaling events and gene expression in multiple cell types of the tumor microenvironment, which could contribute to angiogenesis and altered immunogenic responses in ovarian cancer.
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