Promoter hypermethylation of the tumor-suppressor genes ITIH5, DKK3, and RASSF1A as novel biomarkers for blood-based breast cancer screening

Table 5 Sensitivity and specificity of breast cancer detection with different marker combinations

	Sensitivity in breast cancer		Specificity in healthy and benign breast disease controls		Pvalue^b	AUC (95% CI)	PPV	NPV
Gene^a	Methylation positive	%	Methylation negative	%			%	%
RASSF1A ITIH5	75 of 138	54	127 of 174	73	7.8 × e^-6	0.647 (0.585-0.709)	61	67
RASSF1A DKK3	82 of 138	59	131 of 174	75	1.6 × e^-8	0.686 (0.626-0.747)	66	70
DKK3 ITIH5	55 of 138	40	164 of 174	94	1.6 × e^-7	0.673 (0.611-0.735)	85	66
RASSF1A DKK3 ITIH5	92 of 138	67	125 of 174	72	1.3 × e ^-10	0.712 (0.653-0.770)	65	73

^aEither gene methylated. ^bFisher Exact test at a two-sided significance level of 0.05. AUC, area under the curve; CI, confidence interval; NPV, negative predictive value; PPV, positive predictive value.

ISSN: 1465-542X