Evidence map›Paper›PMID 38890593›Full record

ArticleBMC cancer2024

Oral pimonidazole unveils clinicopathologic and epigenetic features of hypoxic tumour aggressiveness in localized prostate cancer.

Xinpei Ci, Sujun Chen, Rui Zhu, Mojgan Zarif, Rahi Jain, Wangyuan Guo, Matthew Ramotar, Linsey Gong, Wenjie Xu, Olivia Singh and 9 more

Abstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Article
  5. From Hypoxia to Bone: Reprogramming the Prostate Cancer Metastatic Cascade.International journal of molecular sciences · 2025
    Review
  6. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors.

Xinpei Ci *Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Sujun Chen *Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Rui Zhu *Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Mojgan ZarifPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Rahi JainPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Wangyuan GuoPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Matthew RamotarPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Linsey GongPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Wenjie XuMOE Key Laboratory of Metabolism and Molecular Medicine and Department of Biochemistry and Molecular Biology of School of Basic Medical Sciences, and Fudan University Shanghai Cancer Center, Shanghai Medical College of Fudan University, Shanghai, China.
Olivia SinghPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Sheila MansouriPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Gelareh ZadehPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Gong-Hong WeiMOE Key Laboratory of Metabolism and Molecular Medicine and Department of Biochemistry and Molecular Biology of School of Basic Medical Sciences, and Fudan University Shanghai Cancer Center, Shanghai Medical College of Fudan University, Shanghai, China.
Wei XuPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Robert BristowDivision of Cancer Sciences, University of Manchester, Manchester, UK.
Alejandro BerlinPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada. alejandro.berlin@rmp.uhn.ca.
Marianne KoritzinskyPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada. marianne.koritzinsky@uhnresearch.ca.
Theodorus van der KwastPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada. theodorus.vanderkwast@uhn.ca.
Housheng Hansen HePrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada. hansenhe@uhnresearch.ca.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

DNA MethylationEpigenesis, GeneticNitroimidazolesProstatectomyProstatic NeoplasmsAdministration, OralAgedBiomarkers, TumorHumansMaleMiddle AgedPrognosisTumor HypoxiaBiomarkers, TumorNitroimidazolespimonidazoleBiomarkerDNA MethylationHypoxiaPIMOProstate Cancer

Identifiers

PMID38890593
PMCPMC11186205

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.