ArticleCell death & disease2021
Interrogation of gender disparity uncovers androgen receptor as the transcriptional activator for oncogenic miR-125b in gastric cancer.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 22 citations in OpenAlex.
- Associations between serum sex steroid hormone metabolites and gastric cancer and precancerous lesions in men: A 11.8-year prospective study.Journal of translational internal medicine · 2025Article
- Patient-derived xenograft models: Current status, challenges, and innovations in cancer research.Genes & diseases · 2025Review
- Transcription factors and hormone receptors: Sex‑specific targets for cancer therapy (Review).Oncology letters · 2025Review
- Sex bias in tumor immunity: insights from immune cells.Theranostics · 2025Review
- Aging-induced immune microenvironment remodeling fosters melanoma in male mice via γδ17-Neutrophil-CD8 axis.Nature communications · 2024Article
- Sex difference in human diseases: mechanistic insights and clinical implications.Signal transduction and targeted therapy · 2024Review
- The implication of integrative multiple RNA modification-based subtypes in gastric cancer immunotherapy and prognosis.iScience · 2024Article
- Gender Differences and miRNAs Expression in Cancer: Implications on Prognosis and Susceptibility.International journal of molecular sciences · 2023Review
- Generation, evolution, interfering factors, applications, and challenges of patient-derived xenograft models in immunodeficient mice.Cancer cell international · 2023Review
- Stranger Things: New Roles and Opportunities for Androgen Receptor in Oncology Beyond Prostate Cancer.Endocrinology · 2023Review
- Comprehensive analysis of autophagy-related clusters and individual risk model for immunotherapy response prediction in gastric cancer.Frontiers in oncology · 2023Article
- Advances in sex disparities for cancer immunotherapy: unveiling the dilemma of Yin and Yang.Biology of sex differences · 2022Review
- The integrated landscape of eRNA in gastric cancer reveals distinct immune subtypes with prognostic and therapeutic relevance.iScience · 2022Article
- The sex-dependent role of the androgen receptor in glioblastoma: results of molecular analyses.Molecular oncology · 2022Article
- Patient-Derived Xenograft: A More Standard "Avatar" Model in Preclinical Studies of Gastric Cancer.Frontiers in oncology · 2022Review
- Machine Learning for Future Subtyping of the Tumor Microenvironment of Gastro-Esophageal Adenocarcinomas.Cancers · 2021Review
- Characterization of Two Ferroptosis Subtypes With Distinct Immune Infiltration and Gender Difference in Gastric Cancer.Frontiers in nutrition · 2021Article
- Identification of an m6A Regulators-Mediated Prognosis Signature For Survival Prediction and Its Relevance to Immune Infiltration in Melanoma.Frontiers in cell and developmental biology · 2021Article
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Authors and funding
20 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
There is a male preponderance in gastric cancer (GC), which suggests a role of androgen and androgen receptor (AR). However, the mechanism of AR signaling in GC especially in female patients remains obscure. We sought to identify the AR signaling pathway that might be related to prognosis and examine the potential clinical utility of the AR antagonist for treatment. Deep learning and gene set enrichment analysis was used to identify potential critical factors associated with gender bias in GC (n = 1390). Gene expression profile analysis was performed to screen differentially expressed genes associated with AR expression in the Tianjin discovery set (n = 90) and TCGA validation set (n = 341). Predictors of survival were identified via lasso regression analyses and validated in the expanded Tianjin cohort (n = 373). In vitro and in vivo experiments were established to determine the drug effect. The GC gender bias was attributable to sex chromosome abnormalities and AR signaling dysregulation. The candidates for AR-related gene sets were screened, and AR combined with miR-125b was associated with poor prognosis, particularly among female patients. AR was confirmed to directly regulate miR-125b expression. AR-miR-125b signaling pathway inhibited apoptosis and promoted proliferation. AR antagonist, bicalutamide, exerted anti-tumor activities and induced apoptosis both in vitro and in vivo, using GC cell lines and female patient-derived xenograft (PDX) model. We have shed light on gender differences by revealing a hormone-regulated oncogenic signaling pathway in GC. Our preclinical studies suggest that AR is a potential therapeutic target for this deadly cancer type, especially in female patients.
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