Investig Clin Urol.  2019 Nov;60(6):425-431. 10.4111/icu.2019.60.6.425.

Prolyl hydroxylase-3 is a novel renal cell carcinoma biomarker

  • 1Department of Urology, Ewha Womans University College of Medicine, Seoul, Korea.
  • 2Department of Urology, National Health Insurance Service Ilsan Hospital, Goyang, Korea.
  • 3Department of Urology, Hanyang University College of Medicine, Seoul, Korea.
  • 4Department of Urology, Urological Science Institute, Yonsei University College of Medicine, Seoul, Korea.
  • 5Department of Biochemistry and Molecular Biology, Institute of Genetic Science, Integrated Genomic Research Center for Metabolic Regulation, Yonsei University College of Medicine, Seoul, Korea.
  • 6Brain Korean 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.


The aim of this study was to determine the suitability of serum prolyl hydroxylase-3 (PHD3) as a diagnostic or monitoring biomarker of renal cell carcinoma (RCC).
Between October 2013 and March 2015, we prospectively recruited study participants. The RCC group consisted of 56 patients who underwent radical or partial nephrectomy. The control group included 56 healthy kidney donors and 13 patients with benign renal masses. Blood from the RCC patients was sampled prior to surgery and again 1 and 3 months after the operation. Serum PHD3 levels were measured via enzyme-linked immunosorbent assay and compared between RCC patients and controls.
RCC patients had higher serum PHD3 levels than controls (0.79±0.17 ng/mL vs. 0.73±0.09 ng/mL, p=0.023), with an area under curve (AUC) of 0.668. With a cutoff value of 0.761 ng/ml, the sensitivity, specificity, positive predictive value, and negative predictive value were 66.1%, 68.1%, 28.8%, and 37.3%, respectively. No significant difference in PHD3 level was observed between healthy kidney donors and patients with benign renal masses. The predictive performance of PHD3 was improved in subgroup analyses of RCC patients with a tumor size >2 cm (n=40) or clear-cell histology (n=44), with AUCs of 0.709 and 0.688, respectively. Among 37 patients with PHD3 levels greater than the cutoff value of 0.761 ng/mL, the postoperative PHD3 levels at 1 and 3 months were significantly lower than the preoperative PHD3 levels (both p<0.001).
Serum PHD3 represents a novel RCC biomarker that shows acceptable diagnostic performance.


Area under curve; Carcinoma, renal cell; Early diagnosis; Nephrectomy

MeSH Terms

Area Under Curve
Carcinoma, Renal Cell*
Early Diagnosis
Enzyme-Linked Immunosorbent Assay
Prospective Studies
Sensitivity and Specificity
Tissue Donors
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