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Decreased prolyl hydroxylase 3 mRNA expression in oncocytomas compared with clear cell renal cell carcinoma
Spyridon Kampantais1,2, Ilias Kounatidis3,4, Vasiliki Kotoula5
11st Department of Urology, Gennimatas General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.
Introduction:
Hypoxia inducible factors (HIF) and prolyl hydroxylase domain (PHD) enzymes play a central role in tumor progression in clear cell renal cell carcinoma (ccRCC). However, there are currently no data regarding the behavior of this pathway (HIF/PHD) in a large number of benign renal tumors, the oncocytomas. The aim of the present study was to compare the expression levels of these factors between ccRCC and oncocytoma tumors.
Material And Methods:
A total of 56 fresh frozen specimens from patients with ccRCC and 14 oncocytoma specimens were analyzed via reverse transcription-quantitative polymerase chain reaction in order to assess the expression levels of HIF-1α, HIF-2α, PHD1, PHD2, and PHD3. The analysis involved both fresh frozen tumor samples as well as adjacent normal kidney tissues.
Results:
In ccRCC, HIF-1α and HIF-2α levels were upregulated in 65.5% and 71.4% of cases, respectively. PHD3 was downregulated only in 15.4% of the ccRCC cases, in contrast with oncocytoma cases, which exhibited low expression levels in the majority. The upregulation of PHD3 messenger RNA (mRNA) levels in ccRCC when compared with oncocytoma was statistically significant (P<0.001). No other comparisons (HIF-1α, HIF-2α, PHD1, and PHD2) were significantly different. HIF-2α and PHD3 mRNA expression levels were negatively correlated with Fuhrman Grade (P=0.029 and P=0.026, respectively) in ccRCC.
Conclusion:
To the best of our knowledge, this is the first time that the HIF/PHD pathway was compared between ccRCC and a common benign tumor, identifying the upregulation of PHD3 as the possible underlying factor guiding the difference in the behavior of ccRCC.
Insights
The hypoxia-inducible factor (HIF) and prolyl hydroxylase domain (PHD) pathway differs between clear cell renal cell carcinoma (ccRCC) and oncocytoma. Upregulation of PHD3 mRNA in ccRCC suggests its role in ccRCC tumor behavior.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Hypoxia-inducible factors (HIF) and prolyl hydroxylase domain (PHD) enzymes are crucial in clear cell renal cell carcinoma (ccRCC) progression.
- Limited data exist on the HIF/PHD pathway in benign renal tumors, specifically oncocytomas.
- Understanding these pathways is key to differentiating ccRCC from benign tumors.
Purpose of the Study:
- To compare the expression levels of HIF-1α, HIF-2α, PHD1, PHD2, and PHD3 between ccRCC and oncocytoma.
- To investigate the role of the HIF/PHD pathway in distinguishing ccRCC from oncocytoma.
Main Methods:
- Analysis of 56 ccRCC and 14 oncocytoma fresh frozen specimens.
- Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) used to assess mRNA expression levels.
- Comparison between tumor tissues and adjacent normal kidney tissues.
Main Results:
- HIF-1α and HIF-2α were upregulated in 65.5% and 71.4% of ccRCC cases, respectively.
- PHD3 was downregulated in only 15.4% of ccRCC cases, contrasting with high expression in most oncocytomas.
- PHD3 mRNA upregulation in ccRCC compared to oncocytoma was statistically significant (P<0.001); HIF-2α and PHD3 mRNA levels negatively correlated with Fuhrman Grade in ccRCC.
Conclusions:
- This study is the first to compare the HIF/PHD pathway between ccRCC and oncocytoma.
- PHD3 upregulation may be a key factor differentiating ccRCC from oncocytoma.
- Findings suggest PHD3's potential role in ccRCC tumor behavior and progression.
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