Table 2 DNA hypermethylation markers evaluated as binary marker (positive or negative) based on two statistical approaches (Youden’s J index and fixed specificity) with different threshold setting on learning set (A) and subsequent evaluation on validation set (B)

From: DNA hypermethylation analysis in sputum for the diagnosis of lung cancer: training validation set approach

  AUC 95% CI Sensitivity (%) 95% CI (%) Specificity (%) 95% CI P -values
A. Learning set
Cutoff based on Youden’s J index        
 RASSF1A 0.69 0.60–0.77 42.5 31.0–54.6 96.5 90.1–99.3 <0.001
 APC 0.64 0.55–0.73 52.1 40.0–63.9 70.9 60.1–80.2 0.003
 CYGB 0.65 0.56–0.74 56.2 44.1–67.8 74.4 63.9–83.2 <0.001
 3OST2 0.72 0.64–0.80 50.7 38.7–62.6 86.0 76.9–92.6 <0.001
 PRDM14 0.71 0.63–0.79 60.3 48.1–71.5 76.7 66.4–85.2 <0.001
 FAM19A4 0.59 0.50–0.68 86.3 76.2–93.2 29.1 19.8–39.9 0.02
 PHACTR3 0.69 0.61–0.77 57.5 45.4–69.0 77.9 67.7–86.1 <0.001
 RASSF1A, 3OST2 and PRDM14    82.2 71.5–90.2 66.3 55.3–76.1 <0.001
Cutoff based on fixed specificity of >96% in learning set        
 RASSF1A    42.5 31.0–54.6 96.5 90.1–99.3 <0.001
 APC    16.4 8.8–27.0 96.5 90.1–99.3 0.005
 CYGB    19.2 10.9–30.1 96.5 90.1–99.3 0.001
 3OST2    31.5 21.1–43.4 96.5 90.1–99.3 <0.001
 PRDM14    17.8 9.8–28.5 96.5 90.1–99.3 0.003
 FAM19A4    15.1 7.8–25.4 96.5 90.1–99.3 0.01
 PHACTR3    28.8 18.8–40.6 96.5 90.1–99.3 <0.001
 RASSF1A, 3OST2 and PHACTR3    67.1 55.1–77.7 89.5 90.1–99.3 <0.001
B. Validation set
Cutoff based on Youden’s J index        
 RASSF1A 0.67 0.61–0.73 36.5 29.0–44.5 88.3 82.2–92.9 <0.001
 APC 0.63 0.57–0.69 52.2 44.1–60.2 69.5 61.676.6 <0.001
 CYGB 0.64 0.58–0.70 49.7 41.7–57.7 68.2 60.2–75.4 0.001
 3OST2 0.71 0.65–0.77 49.7 41.7–57.7 85.1 78.4–90.3 <0.001
 PRDM14 0.75 0.69–0.80 64.8 56.8–72.2 74.0 66.4–80.8 <0.001
 FAM19A4 0.66 0.59–0.72 77.4 70.1–83.6 22.1 15.8–29.5 0.90
 PHACTR3 0.67 0.61–0.73 60.4 52.3–68.0 62.3 54.2–70.0 <0.001
 RASSF1A, 3OST2 and PRDM14    79.2 72.1–85.3 64.3 56.2–71.8 <0.001
Cutoff based on fixed specificity of >96% in learning set        
 RASSF1A    36.5 29.0–44.5 88.3 82.2–92.9 <0.001
 APC    22.0 15.8–29.3 96.8 92.6–98.9 <0.001
 CYGB    19.5 13.6–26.5 98.1 94.4–99.6 <0.001
 3OST2    34.0 26.6–41.9 96.8 92.6–98.9 <0.001
 PRDM14    27.0 20.3–34.7 96.8 92.6–98.9 <0.001
 FAM19A4    26.4 19.7–34.0 97.4 93.5–99.3 <0.001
 PHACTR3    25.2 18.6–32.6 91.6 86.0–95.4 <0.001
 RASSF1A, 3OST2 and PHACTR3    64.8 56.8–72.2 80.5 73.4–86.5 <0.001
  1. Abbreviations: AUC=area under the curve; 95% CI=95% confidence intervals.
  2. AUC and 95% CI were calculated for the learning set. Combination rules were defined using multivariate logistic regression. P-values are given for the statistical difference between cases and controls.