Serum cell‐free DNA in renal cell carcinoma

Abstract

BACKGROUND: Currently, there are no established diagnostic and prognostic serum markers for renal cell carcinoma (RCC). The objective of this study was to evaluate the putative significance of serum cell-free DNA. METHODS: Preoperative serum samples from 200 consecutive patients with sporadic, solid renal tumors were analyzed (157 patients with RCC and 43 patients with benign renal tumors). Quantitative real-time polymerase chain reaction was used to assess total cell-free DNA (ring finger protein 185 [RNF185]) and CpG island methylation of Ras association domain family member 1A (RASSF1A) von Hippel-Lindau (VHL), prostaglandin-endoperoxidase synthase 2 (PTGS2), and P16 (cyclin-dependent kinase inhibitor 2A). Associations with RCC, pathologic variables, and disease-specific survival were evaluated. RESULTS: Total cell-free DNA levels and CpG island methylation of RASSF1A and VHL were highly diagnostic for RCC with an area under the receiver operating characteristic curve of 0.755, 0.705, and 0.694, respectively. VHL methylation was detected more frequently in patients with clear cell RCC than in those with other subtypes (P ¼ .007). Total cell-free DNA levels were higher in patients with metastatic RCC (P < .001) and necrotic RCC (P ¼ .003) and were associated with poorer disease-specific survival (P < .001). In multivariate analysis, the tumor stage, size, grade, and necrosis (SSIGN) score (P < .001) and categorized total cell-free DNA levels (P ¼ .028) were retained as independent prognostic factors. CONCLUSIONS: The current results indicated that cell-free DNA represents a novel serum-based diagnostic and prognostic biomarker for RCC. Total serum cell-free DNA levels and CpG island methylation of RASSF1A and VHL may be useful diagnostic biomarkers for RCC. VHL methylation of cellfree DNA is suggestive of clear cell RCC. Total serum cell-free DNA may be a useful prognostic biomarker that may assist in tailoring postoperative surveillance and therapy. External prospective validation of these data will be required. Cancer 2012;118:82-

Monitoring of Plasma Cell-Free DNA in Predicting Postoperative Recurrence of Clear Cell Renal Cell Carcinoma

“…Circulating cfDNA, a biomarker that is easily accessible and preferably noninvasive, has been shown to have diagnostic and prognostic potential in RCC [12,19]. As necrosis is the predominant type of cell death in tumor tissue, longer DNA fragments representing non-apoptotic DNA may be a suitable marker in cancer.…”

Circulating Cell-Free DNA Levels in Patients with Metastatic Renal Cell Carcinoma

“…First, CFD elevation is not specific for RCC. Elevated CFD levels have been observed in patients with different types of malignancies [6][7][8] as well as nonmalignant etiologies, such as trauma, systemic inflammatory disorders, pulmonary embolism, and acute myocardial infarction [11]. Second, the present study cohort is small and heterogeneous (mixed first and advanced treatment lines) and, thus, in a larger and homogeneous cohort, other factors might have been associated with treatment outcome.…”

New Progress of Epigenetic Biomarkers in Urological Cancer

“…The results indicated that Wnt antagonist family genes detection had sensitivity of 79.0% and specificity of 75.8% and the serum DNA was significantly correlated with tumor grade and stage [36]. Besides, other studies have reported that some genes are highly specific for RCC patients in the level of DNA hypermethylation including VHL (91%) and RASSF1A (93%) [37]. Recently, another similar outcome showed that two genes, SMPD3 and FBXW10, are hypermethylated in ccRCC tissue samples compared with paired normal tissues.…”