ArticleFrontiers in oncology2021
Identification of a Hypoxia-Related Molecular Classification and Hypoxic Tumor Microenvironment Signature for Predicting the Prognosis of Patients with Triple-Negative Breast Cancer.
Article in Frontiers in oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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20 citing papers in PubMed, 31 citations in OpenAlex.
- Genetic risk and clinical implications of BRCA1 and BRCA2 mutations in Turkish triple-negative breast cancer patients.Discover oncology · 2025Article
- Tumor Hypoxia: How Conventional Histology Is Reshaped in Breast Carcinoma.International journal of molecular sciences · 2025Review
- Insight into the Regulation of NDRG1 Expression.International journal of molecular sciences · 2025Review
- Defining hypoxia in cancer: A landmark evaluation of hypoxia gene expression signatures.Cell genomics · 2025Article
- The platelet-related genes associated with the prognosis of HCC by regulating cycling T cell and prolif-TAMs.Heliyon · 2024Article
- ZC3H12A inhibits tumor growth and metastasis of breast cancer under hypoxic condition via the inactivation of IL-17 signaling pathway.Cell cycle (Georgetown, Tex.) · 2024Article
- A novel model associated with tumor microenvironment on predicting prognosis and immunotherapy in triple negative breast cancer.Clinical and experimental medicine · 2023Article
- Construction of subtype classifiers and validation of a prognostic risk model based on hypoxia-associated lncRNAs for lung adenocarcinoma.Journal of thoracic disease · 2023Article
- Molecular Imaging of Oxygenation Changes during Immunotherapy in Combination with Paclitaxel in Triple Negative Breast Cancer.Biomedicines · 2023Article
- Hypoxia: syndicating triple negative breast cancer against various therapeutic regimens.Frontiers in oncology · 2023Review
- Overview of triple negative breast cancer prognostic signatures in the context of data science-driven clinico-genomics research.Annals of translational medicine · 2022Article
- The Role of the Hypoxia-Related Unfolded Protein Response (UPR) in the Tumor Microenvironment.Cancers · 2022Review
- Adaptation to Hypoxia May Promote Therapeutic Resistance to Androgen Receptor Inhibition in Triple-Negative Breast Cancer.International journal of molecular sciences · 2022Review
- Identification of ubiquitination-related gene classification and a novel ubiquitination-related gene signature for patients with triple-negative breast cancer.Frontiers in genetics · 2022Article
- Computed Tomography Imaging-Based Radiogenomics Analysis Reveals Hypoxia Patterns and Immunological Characteristics in Ovarian Cancer.Frontiers in immunology · 2022Article
- A Novel Defined Hypoxia-Related Gene Signature for Prognostic Prediction of Patients With Ewing Sarcoma.Frontiers in genetics · 2022Article
- A novel risk model based on immune response predicts clinical outcomes and characterizes immunophenotypes in triple-negative breast cancer.American journal of cancer research · 2022Article
- A novel hypoxia- and lactate metabolism-related signature to predict prognosis and immunotherapy responses for breast cancer by integrating machine learning and bioinformatic analyses.Frontiers in immunology · 2022Article
- MLSP: A bioinformatics tool for predicting molecular subtypes and prognosis in patients with breast cancer.Computational and structural biotechnology journal · 2022Article
- A Novel Assessment Model Based on Molecular Subtypes of Hypoxia-Related LncRNAs for Prognosis of Bladder Cancer.Frontiers in cell and developmental biology · 2021Article
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Authors and funding
5 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
purposeThe hypoxic tumor microenvironment was reported to be involved in different tumorigenesis mechanisms of triple-negative breast cancer (TNBC), such as invasion, immune evasion, chemoresistance, and metastasis. However, a systematic analysis of the prognostic prediction models based on multiple hypoxia-related genes (HRGs) has not been established in TNBC before in the literature. We aimed to develop and verify a hypoxia gene signature for prognostic prediction in TNBC patients.
methodsThe RNA sequencing profiles and clinical data of TNBC patients were generated from the TCGA, GSE103091, and METABRIC databases. The TNBC-specific differential HRGs (dHRGs) were obtained from differential expression analysis of hypoxia cultured TNBC cell lines compared with normoxic cell lines from the GEO database. Non-negative matrix factorization (NMF) method was then performed on the TNBC patients using the dHRGs to explore a novel molecular classification on the basis of the dHRG expression patterns. Prognosis-associated dHRGs were identified by univariate and multivariate Cox regression analysis to establish the prognostic risk score model.
resultsBased on the expressions of 205 dHRGs, all the patients in the TCGA training cohort were categorized into two subgroups, and the patients in Cluster 1 demonstrated worse OS than those in Cluster 2, which was validated in two independent cohorts. Additionally, the effects of somatic copy number variation (SCNV), somatic single nucleotide variation (SSNV), and methylation level on the expressions of dHRGs were also analyzed. Then, we performed Cox regression analyses to construct an HRG-based risk score model (3-gene dHRG signature), which could reliably discriminate the overall survival (OS) of high-risk and low-risk patients in TCGA, GSE103091, METABRIC, and BMCHH (qRT-PCR) cohorts.
conclusionsIn this study, a robust predictive signature was developed for patients with TNBC, indicating that the 3-gene dHRG model might serve as a potential prognostic biomarker for TNBC.
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