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.

中文翻译：

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与透明细胞肾细胞癌相比，嗜酸细胞瘤中脯氨酰羟化酶 3 mRNA 表达降低

介绍：

缺氧诱导因子 (HIF) 和脯氨酰羟化酶结构域 (PHD) 酶在透明细胞肾细胞癌 (ccRCC) 的肿瘤进展中起核心作用。然而，目前还没有关于该通路 (HIF/PHD) 在大量良性肾肿瘤、嗜酸细胞瘤中的行为的数据。本研究的目的是比较 ccRCC 和嗜酸细胞瘤肿瘤之间这些因子的表达水平。

材料与方法：

通过逆转录-定量聚合酶链反应对来自 ccRCC 患者的 56 个新鲜冷冻标本和 14 个嗜酸细胞瘤标本进行分析，以评估 HIF-1α、HIF-2α、PHD1、PHD2 和 PHD3 的表达水平。该分析涉及新鲜冷冻肿瘤样本以及邻近的正常肾组织。

结果：

在 ccRCC 中，HIF-1α 和 HIF-2α 水平分别在 65.5% 和 71.4% 的病例中上调。PHD3 仅在 15.4% 的 ccRCC 病例中下调，而嗜酸细胞瘤病例在大多数情况下表现出低表达水平。与嗜酸细胞瘤相比，ccRCC 中 PHD3 信使 RNA (mRNA) 水平的上调具有统计学意义（P <0.001）。没有其他比较（HIF-1α、HIF-2α、PHD1 和 PHD2）有显着差异。ccRCC 中 HIF-2α 和 PHD3 mRNA 表达水平与 Fuhrman 等级呈负相关（分别为P = 0.029 和P = 0.026）。

结论：

据我们所知，这是首次比较 ccRCC 和常见良性肿瘤之间的 HIF/PHD 通路，确定 PHD3 的上调可能是指导 ccRCC 行为差异的潜在因素。