Smoking-associated DNA methylation markers predict lung cancer incidence

Clinical Epigenetics

Table 4 Individual and joint discriminative performance of methylation at AHRR, 6p21.33, and F2RL3

Group	AUC (95% CI)
Group	AHRR_cg05575921	6p21.33_cg06126421	F2RL3_cg03636183	Combination^a
Overall
Training set (n = 78 cases)	0.792 (0.736–0.848)	0.662 (0.597–0.726)	0.791 (0.735–0.846)	0.829 (0.778–0.881)
Validation set (n = 65 cases)	0.799 (0.733–0.866)	0.789 (0.725–0.853)	0.812 (0.725–0.871)	0.800 (0.737–0.861)
Age specific prediction
<65 years (n = 77 cases)	0.789 (0.728–0.850)	0.745 (0.687–0.803)	0.792 (0.735–0.849)	0.800 (0.745–0.856)
≥65 years (n = 66 cases)	0.790 (0.726–0.856)	0.677 (0.604–0.751)	0.793 (0.732–0.854)	0.817 (0.760–0.875)
Follow-up time-specific prediction
Initial 5 years (n = 68 cases)	0.791 (0.733–0.849)	0.696 (0.631–0.761)	0.808 (0.758–0.857)	0.812 (0.759–0.865)
Later years (n = 75 cases)	0.791 (0.734–0.849)	0.730 (0.673–0.786)	0.779 (0.722–0.837)	0.807 (0.755–0.859)
Histological subtype prediction
SCLC (n = 22 cases)	0.744 (0.630–0.858)	0.651 (0.535–0.767)	0.738 (0.632–0.843)	0.739 (0.634–0.844)
NSCLC (n = 119 cases)	0.802 (0.758–0.847)	0.721 (0.672–0.770)	0.798 (0.754–0.843)	0.823 (0.782–0.864)
Adenocarcinoma (n = 48 cases)	0.814 (0.751–0.877)	0.730 (0.659–0.800)	0.814 (0.751–0.876)	0.830 (0.770–0.891)
Squamous cell carcinoma (n = 38 cases)	0.787 (0.709–0.864)	0.731 (0.655–0.807)	0.769 (0.699–0.839)	0.786 (0.717–0.856)
Others (n = 32 cases)	0.775 (0.686–0.864)	0.673 (0.576–0.770)	0.800 (0.713–0.888)	0.813 (0.729–0.896)

Abbreviations: AUC areas under the curve, CI confidence interval, SCLC small cell lung cancer, NSCLC non-small cell lung cancer
^aCombination formula: β1 × M _AHRR + β2 × M _6p21.33 + β3 × M _F2RL3 + β4 × M _6p21.33 × β3 × M _F2RL3 = (−0.0685) × cg05575921 + 0.4673 × cg06126421 + 0.3173 × cg03636183 + (−0.00612) × cg06126421 × cg03636183, where underlined coefficients were derived from regression coefficients in training set

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