ArticleFrontiers in immunology2021
An Eight-Gene Hypoxia Signature Predicts Survival in Pancreatic Cancer and Is Associated With an Immunosuppressed Tumor Microenvironment.
Article in Frontiers in immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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33 citing papers in PubMed, 43 citations in OpenAlex.
- Dual-oxygen pancreatic cancer organoids recapitulate basal-classical heterogeneity validated by spatial transcriptomics.British journal of cancer · 2026Article
- Advances in deciphering intratumoral versus peritumoral heterogeneity of infiltrating lymphocytes in pancreatic cancer: a spatial perspective.Translational oncology · 2026Review
- ITPP in early pancreatic zebrafish xenografts mildly impacts tumor cell death without interfering with vascular normalization.BMC cancer · 2026Article
- Hypoxic Tumor Microenvironment Targeting: Opportunities and Challenges for Pancreatic Cancer Immunotherapy.International journal of molecular sciences · 2026Review
- Multi-omics exploration of hypoxia in gastric cancer.World journal of surgical oncology · 2026Article
- Identification and validation of a hypoxia- and immune-related prognostic signature for pancreatic cancer.Biochemistry and biophysics reports · 2025Article
- Salmonella Typhi gut invasion drives hypoxic immune subsets associated with disease outcomes.Nature communications · 2025Article
- A micro-metabolic rewiring assay for assessing hypoxia-associated cancer metabolic heterogeneity.Bioactive materials · 2025Article
- Integrative systems-level analysis reveals a contextual crosstalk between hypoxia and global metabolism in human breast tumors.Molecular oncology · 2025Article
- P4HA1 Mediates Hypoxia-Induced Invasion in Human Pancreatic Cancer Organoids.Cancer research communications · 2025Article
- Defining hypoxia in cancer: A landmark evaluation of hypoxia gene expression signatures.Cell genomics · 2025Article
- Targeting Hypoxia-Inducible Factor-1α in Pancreatic Cancer: siRNA Delivery Using Hyaluronic Acid-Displaying Nanoparticles.Pharmaceutics · 2024Article
- A Novel Pancreatic Cancer Hypoxia Status Related Gene Signature for Prognosis and Therapeutic Responses.Molecular biotechnology · 2024Review
- Onward Spread from Liver Metastases Is a Major Cause of Multi-Organ Metastasis in a Mouse Model of Metastatic Colon Cancer.Cancers · 2024Article
- High hypoxia status in pancreatic cancer is associated with multiple hallmarks of an immunosuppressive tumor microenvironment.Frontiers in immunology · 2024Article
- Hypoxia at 3D organoid establishment selects essential subclones within heterogenous pancreatic cancer.Frontiers in cell and developmental biology · 2024Article
- Identification of potential prognostic biomarkers among gene models for coiled-coil domain-containing family members in hepatocellular carcinoma elucidates their influence on the hypoxia pathway and immune microenvironment.Journal of gastrointestinal oncology · 2023Article
- CD8 + T cell infiltration is associated with improved survival and negatively correlates with hypoxia in clear cell ovarian cancer.Scientific reports · 2023Article
- Glioblastoma glycolytic signature predicts unfavorable prognosis, immunological heterogeneity, and ENO1 promotes microglia M2 polarization and cancer cell malignancy.Cancer gene therapy · 2023Article
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Authors and funding
9 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Intratumoral hypoxia is a widely established element of the pancreatic tumor microenvironment (TME) promoting immune escape, tumor invasion, and progression, while contributing to treatment resistance and poor survival. Despite this critical role, hypoxia is underrepresented in molecular signatures of pancreatic ductal adenocarcinoma (PDA) and concurrent investigations into the hypoxia-immune status are lacking. In this work a literature-based approach was applied to derive an eight-gene hypoxia signature that was validated in fourteen cancer cell lines and in a cohort of PDA. The eight-gene hypoxia signature was significantly associated with overall survival in two distinct PDA datasets and showed independent prognostic value in multivariate analysis. Comparative analysis of tumors according to their hypoxia score (high versus low) determined that tumors with high hypoxia were significantly less enriched in cytotoxic T-cells, and cytolytic activity. In addition, they had lower expression of cytokines and tumor inflammatory markers, pointing to the signature's ability to discern an immune "cold", hypoxic TME. Combining the signature with an immune metric highlighted a worse survival probability in patients with high hypoxia and low immune reactivity, indicating that this approach could further refine survival estimates. Hypoxia as determined by our signature, was significantly associated with certain immune checkpoint inhibitors (ICI) biomarkers, suggesting that the signature reflects an aspect of the TME that is worth pursuing in future clinical trials. This is the first work of its kind in PDA, and our findings on the hypoxia-immune tumor contexture are not only relevant for ICI but could also guide combinatorial hypoxia-mediated therapeutic strategies in this cancer type.
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