Table 3

Sensitive detection of cancer in urine sediment and serum DNA of RCCa patients using DNA methylation markers

Analytical sensitivity defined as the fraction of cases in which methylation of a marker is found in urine or serum for cases with confirmed methylation of the same marker in the associated tumor [e.g., in Table 2 <$REFLINK> , the frequency of APC methylation in primary tumors is 29% (5/17); of these 5 methylated cases, methylation was detected in the urine of 4 patients; therefore, the analytical sensitivity is 80% (4/5)]. Clinical sensitivity is defined as the fraction of confirmed cases of disease, in which methylation of a marker is found in urine or serum, regardless of whether methylation of that marker is present in the associated tumor or regardless of whether the associated tumor has been analyzed for the presence of the marker. Cases in which urine or serum is not analyzed are excluded from both sensitivity calculations. Specificity is defined as the fraction of controls without the disease that show a lack of detectable methylation in urine or serum.

DiseaseDNA sourceMarkersAnalytical sensitivity (%)Clinical sensitivity (%)Specificity (%)Cutoff values
Renal cancerUrine APC 4/5 (80)10/26 (38)964.5
ARF 3/4 (75)8/26 (31)1000
CDH1 6/10 (60)10/26 (38)950.3
GSTP1 1/2 (50)4/26 (15)1000
MGMT 0/1 (0)2/26 (8)1000
p16 4/6 (67)9/26 (35)1000
RAR-82 4/9 (44)8/26 (31)910.1
RASSF1A 11/15 (73)17/26 (65)890.1
TIMP3 6/12 (50)12/26 (46)911
Serum APC 1/5 (20)1/18 (6)974.5
ARF 1/4 (25)1/18 (6)970
CDH1 6/10 (60)6/18 (33)930.3
GSTP1 0/2 (0)1/18 (6)1000
MGMT 0/1 (0)0/18 (0)970
p16 3/6 (50)4/18 (22)1000
RAR-82 1/9 (11)1/18 (6)1000.1
RASSF1A 2/15 (13)2/18 (11)970.1
TIMP3 2/12 (17)3/18 (17)1001
  • a RCC, renal cell carcinoma.