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

• Kim KH
• Lee HH
• Yoon YE
• Na JC
• Kim KS
• Han WK

• KMID: 2461053
• DOI: http://doi.org/10.4111/icu.2019.60.6.425

Abstract

PURPOSE
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).
MATERIALS AND METHODS
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.
RESULTS
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).
CONCLUSIONS
Serum PHD3 represents a novel RCC biomarker that shows acceptable diagnostic performance.

Keyword

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

MeSH Terms

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

Figure

• 

  Fig. 1 (A) Difference in serum prolyl hydroxylase-3 (PHD3) levels between renal cell carcinoma (RCC) patients and controls. The control group included both healthy kidney donors and patients with benign renal masses. (B) Receiver operating characteristic curve for PHD3 comparing RCC patients (n=56) and controls (n=69). The AUC for PHD3 was 0.668 (95% confidence interval, 0.565–0.769).

• 

  Fig. 2 (A) Serial changes in serum prolyl hydroxylase-3 (PHD3) levels after surgery in all patients. (B) Patients with preoperative serum PHD3 levels >0.761 ng/mL. (B) Preoperative and postoperative PHD3 levels were compared using paired t-test.

• 

  Fig. 3 Data for prolyl hydroxylase-3 (PHD3) expression level from cBioPortal (http://www.cbioportal.org). Cancer types associated with upregulated PHD3 expression were included in the analysis. The median level of PHD3 expression was higher in clear-cell renal cell carcinoma (RCC) than in other types of malignancy.

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