ArticleBMC cancer2024
Oral pimonidazole unveils clinicopathologic and epigenetic features of hypoxic tumour aggressiveness in localized prostate cancer.
Article in BMC cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Beyond EMT: Mesenchymal drift as an emerging driver of stromal-immune reprogramming in prostate cancer.iScience · 2026Review
- Testican-1-MMP axis in tumour extracellular matrix (ECM) remodelling: interaction dynamics analysis and an in silico perspective.The Journal of pathology · 2026Article
- Integrative Whole-Genome and Epigenome Profiling of cfDNA in Familial Prostate Cancer: Insights from a Pilot Study.Biomedicines · 2026Article
- HIF1 inhibition targets tumoral and myeloid cells, and is a promising therapy for metastatic castration-resistant prostate cancer.Cell death & disease · 2026Article
- From Hypoxia to Bone: Reprogramming the Prostate Cancer Metastatic Cascade.International journal of molecular sciences · 2025Review
- Review
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Authors and funding
19 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTumor hypoxia is associated with prostate cancer (PCa) treatment resistance and poor prognosis. Pimonidazole (PIMO) is an investigational hypoxia probe used in clinical trials. A better understanding of the clinical significance and molecular alterations underpinning PIMO-labeled tumor hypoxia is needed for future clinical application. Here, we investigated the clinical significance and molecular alterations underpinning PIMO-labeled tumor hypoxia in patients with localized PCa, in order to apply PIMO as a prognostic tool and to identify potential biomarkers for future clinical translation.
methodsA total of 39 patients with localized PCa were recruited and administered oral PIMO before undergoing radical prostatectomy (RadP). Immunohistochemical staining for PIMO was performed on 37 prostatectomy specimens with staining patterns evaluated and clinical association analyzed. Whole genome bisulfite sequencing was performed using laser-capture of microdissected specimen sections comparing PIMO positive and negative tumor areas. A hypoxia related methylation molecular signature was generated by integrating the differentially methylated regions with previously established RNA-seq datasets.
resultsThree PIMO staining patterns were distinguished: diffuse, focal, and comedo-like. The comedo-like staining pattern was more commonly associated with adverse pathology. PIMO-defined hypoxia intensity was positively correlated with advanced pathologic stage, tumor invasion, and cribriform and intraductal carcinoma morphology. The generated DNA methylation signature was found to be a robust hypoxia biomarker, which could risk-stratify PCa patients across multiple clinical datasets, as well as be applicable in other cancer types.
conclusionsOral PIMO unveiled clinicopathologic features of disease aggressiveness in localized PCa. The generated DNA methylation signature is a novel and robust hypoxia biomarker that has the potential for future clinical translation.
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