mRNA overexpression of prolyl hydroxylase PHD3 is inversely related to nuclear grade in renal cell carcinoma

The aim of the present study was to evaluate the relative mRNA expression levels of genes involved in the hypoxia inducible factor (HIF) signalling pathway in renal cell carcinoma (RCC) and to analyse their associations with clinicopathological parameters and survival outcomes. Reverse transcription-quantitative PCR was used to quantify the mRNA expression levels of HIF-1α, HIF-2α, prolyl hydroxylase (PHD)1, PHD2 and PHD3 in formalin-fixed paraffin-embedded (FFPE) tumour tissue samples from 41 patients with RCC, including 33 cases of clear cell RCC (ccRCC). FFPE samples of corresponding adjacent normal kidney tissues were used as a comparison. mRNA expression levels were analysed in regard to clinical parameters, histological type, stage, nuclear grade, cancer specific survival and overall survival. Compared with adjacent normal kidney tissue, HIF-1α levels were lower in 16/33 ccRCC samples (48.48%), while HIF-2α, PHD1 and PHD2 levels did not exhibit a specific expression pattern. By contrast, the PHD3 mRNA level was higher in 29/33 (87.87%) of the tumour samples. HIF-1α was positively associated with HIF-2α, PHD1 and PHD2. HIF-2α levels were associated with PHD1, PHD2 and PHD3, while PHD3 was strongly associated with PHD2. PHD3 mRNA levels were inversely associated with nuclear grade (P=0.015). However, in univariate analysis, PHD3 was not associated with cancer-specific or overall survival rates. The present findings suggest an important involvement of PHD3 in ccRCC, since PHD3 mRNA expression was inversely associated with nuclear grade. However, PHD3 mRNA levels did not have an independent prognostic value. Further studies are required to investigate whether PHD3 could be used as either a therapeutic target or prognostic marker.