Usefulness of Circulating Methylated p16 as a Noninvasive Molecular Biomarker for Hepatitis C-Related Hepatocellular Carcinoma with Normal Serum Alpha-Fetoprotein Levels

Figures & data

Table 1 Baseline Demographic and Clinical Characteristics of Patients with HCV-Related Chronic Liver Disease

	Patients with HCC (n= 95)	Patients with BLD (n= 105)
Age (years, mean ± SD)	60.8 ± 6.1	58.6 ± 7.8
Sex (n, %)
Male	77 (81.1%)	81 (77.1%)
Female	18 (18.9%)	24 (22.9%)
Severity of Hepatic Disease (n, %)
CHC	–	40 (38.1%)
LC	95 (100%)	65 (61.9%)
Child-Pugh score (mean ± SD)	9.3 ± 2.5	9.6 ± 2.7
MELD score (mean ± SD)	16.7 ± 7.8	16.1 ± 6.5
AFP (n, %)
≤500 ng/mL	38 (40.4%)	105 (100%)
>500 ng/mL	57 (59.6%)	-
Number of HCC (n, %)
Single	40 (42.1%)	–
More than one	55 (57.9%)
Size of HCC (n, %)
≤5 cm	42 (44.2%)	–
>5 cm	53 (55.8%)

Abbreviations: AFP, alpha-fetoprotein; BLD, benign liver disease; CHC, chronic hepatitis C; HCC, hepatocellular carcinoma; LC, liver cirrhosis; MELD, Model of end-stage liver disease; n, number; SD, standard deviation.

Table 2 Distribution of Serum Methylated P16 Levels Among Healthy Controls and Cases

	Cases (n)	Serum Methylated p16 Levels (Median & Range; Fold Changes)	p
Healthy controls	30	1.06 (0.57–1.69)	<0.001
Patients with HCV-related BLD	105	108.34 (0.75–5.5x10^5)^a
Patients with HCV-related HCC	95	760.08 (0.91–1.1x106)^b

Notes: ^aP < 0.001 compared with controls, ^bP = 0.037 compared with BLD.

Abbreviations: BLD, benign liver disease; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; n, number.

Figure 1 Comparison between serum methylated p16 levels among different groups (healthy controls and HCV-related chronic liver disease).

Abbreviations: CHC, chronic hepatitis C; HCC, hepatocellular carcinoma; LC, liver cirrhosis.

Figure 2 Comparison between serum methylated p16 levels among different groups (HCC cases and non-HCC cases).

Abbreviations: AFP, alpha-fetoprotein; HCC, hepatocellular carcinoma.

Figure 3 Area under the receiver operating characteristic curves (AUC) of (A) methylated p16 [AUC= 0.7; 95% CI (0.580–0.772)] for predicting HCC versus non-HCC, (B) combination of methylated p16 and AFP [AUC= 0.872; 95% CI (0.742–0.951)] for predicting HCC versus non-HCC, and (C) methylated p16 [AUC= 0.823; 95% CI (0.694–0.942)] for predicting HCC in patients with hepatic mass and normal AFP versus non-HCC cases.

Abbreviations: AFP, alpha-fetoprotein; HCC, hepatocellular carcinoma.