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Updated: Jul 2, 2025
09:17
Co-immunoprecipitation Assay Using Endogenous Nuclear Proteins from Cells Cultured Under Hypoxic Conditions
Published on: August 2, 2018
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Low nuclear expression of HIF-hydroxylases PHD2/EGLN1 and PHD3/EGLN3 are associated with poor recurrence-free
Lassi Luomala1, Kalle Mattila2,3, Paula Vainio4
1Dept. of Urology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
Cancer Medicine
|February 24, 2024
Summary
Nuclear expression of PHD2 and PHD3 proteins indicates better outcomes for clear cell renal cell carcinoma (ccRCC) patients. These hypoxia-inducible factor regulators are promising biomarkers for predicting ccRCC recurrence-free survival.
Area of Science:
- Oncology
- Molecular Biology
- Biomarker Discovery
Background:
- Hypoxia-inducible factors (HIFs) and their regulators, prolyl hydroxylase domain proteins (PHDs), are crucial in cellular responses to hypoxia.
- These factors play a role in clear cell renal cell carcinoma (ccRCC) progression.
- PHD biomarkers may enhance predictions of disease progression and guide adjuvant treatment decisions for ccRCC.
Purpose of the Study:
- To investigate the association of PHD2 and PHD3 expression with histopathological features and recurrence-free survival (RFS) in localized ccRCC.
- To evaluate PHD2 and PHD3 as potential prognostic biomarkers in ccRCC.
Main Methods:
- Retrospective analysis of 173 patients with localized ccRCC from Helsinki University Hospital (HUH).
- External validation using a cohort of 191 patients from Turku University Hospital (TUH).
- Immunohistochemical staining of tissue microarrays to assess nuclear and cytoplasmic expression of PHD2 and PHD3, correlated with clinical and histopathological data.
Main Results:
- Nuclear expression of PHD2 and PHD3 was associated with lower tumor stage (pT-stage) and Fuhrman grade.
- Patients with positive nuclear PHD2 and PHD3 expression showed favorable RFS compared to those with negative expression.
- Nuclear PHD2 expression independently predicted a reduced risk of disease recurrence or death in multivariable analysis, consistent across both cohorts.
Conclusions:
- Absence of nuclear PHD2 and PHD3 expression in ccRCC correlates with poor RFS.
- Nuclear PHD2 expression is a significant predictor of RFS, independent of other prognostic factors.
- Nuclear PHD2 and PHD3 represent potential prognostic biomarkers for localized ccRCC, warranting further prospective validation.
Keywords:
biomarkerhydroxylase-domain proteins (PHD)hypoxia inducible factors (HIF)recurrence-free survivalrenal cell carcinoma (RCC)More Related Videos
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