Adequate clinical management of small renal tumors (SRTs, <4 cm) is important despite their slow growth and low metastatic potential. Surgical resection or nephrectomy remains the main treatment strategy. However, up to 30% of SRTs suspicious for malignancy by preoperative imaging reveal to be benign on final pathological examination after surgery. Moreover, most incidental tumors are detected in the elderly with comorbidities unsuitable for surgical treatment. Up to date, tumor growth rate is the only parameter determining aggressiveness of unresectable SRTs The study aimed at selection of methylated DNA biomarkers for non-invasive urine-based active surveillance of patients, diagnosed with SRTs.
Urine samples were collected at different time points from the 40 patients diagnosed with SRTs (N=163 in total), as well as 92 asymptomatic controls (ASC). Methylated DNA levels of six candidate biomarkers ZNF677, FBN2, PCDH8, TFAP2B, TAC1, and FLRT2 were evaluated by quantitative methylation-specific PCR. Statistical analysis was done by MedCalc, STATISTICA 8, and GraphPad Prism softwares.
Methylated DNA levels of 4 out of 6 genes were significantly higher in the urine samples of SRTs compared to ASC and PCDH8 was characterized by the highest diagnostic potential (AUC = 0.69) with 63% of sensitivity and 74% of specificity. A combination of 2-3 genes showed slightly higher diagnostic values and the panel of PCDH8, TAC1 & FLRT2 (AUC = 0.73) was the most clinically promising. Moreover, methylated PCDH8 level was significantly correlated with tumor volume (Rs – 0.27; P = 0.006) among gradually growing SRTs, showing its potential for non-invasive monitoring of disease progression.
Urinary level of methylated PCDH8 is a promising biomarker for non-invasive diagnosis of SRTs and prognostic indicator for tumor growth kinetics.
This work was funded by the 2014–2020 European Union Structural Funds according to the activity \"Intelligence. Joint science-business projects” grant No. J05-LVPA-K-04–0029.
S. Jarmalaite.
Thermo Pharma Baltic.
All authors have declared no conflicts of interest.