Serum manganese superoxide dismutase and thioredoxin are potential prognostic markers for hepatitis C virus-related hepatocellular carcinoma

Table 1 Patient clinical characteristics

Characteristics	Non-HCC group(n = 34)	HCC group(n = 30)	P value1
Age (yr)	62.3 ± 11.0	72.2 ± 7.5	< 0.001
Sex (male/female)	10/24	21/9	< 0.01
Plt (× 104/μL)	17.0 ± 5.5	10.3 ± 5.2	< 0.001
PT (%)	99.7 ± 13.3	77.6 ± 11.8	< 0.001
Alb (g/dL)	4.3 ± 0.4	3.6 ± 0.6	< 0.001
T-Bil (mg/dL)	0.8 ± 0.3	1.5 ± 0.8	< 0.001
ALT (IU/L)	44.8 ± 30.2	52.0 ± 28.2	0.12
γ-GTP (IU/L)	31.3 ± 16.1	56.2 ± 44.3	< 0.01
AFP (ng/mL)	7.2 ± 22.8	85.9 ± 197.6	< 0.001
DCP (mAU/mL)	22.8 ± 14.7	485.5 ± 1982.6	0.001
HCV serotype group (1/2)	18/10 (n = 28)	21/3 (n = 24)	0.06
HCV RNA level (high/low)	28/5 (n = 33)	21/4 (n = 25)	0.99

Data are shown as the mean ± SD. n: Number of patients or the number of samples analyzed.

¹Differences between mean values were evaluated using either the Fischer’s exact test or the Mann-Whitney U test, as appropriate. Plt: Platelet count; PT: Prothrombin time; Alb: Albumin; T-Bil: Total bilirubin; ALT: Alanine aminotransferase; γ-GTP: γ-glutamyl transpeptidase; AFP: alpha-fetoprotein; DCP: des-γ-carboxy prothrombin; HCV: Hepatitis C virus; RNA: Ribonucleic acid.

Table 2 Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of manganese superoxide dismutase and α-fetoprotein serum levels for diagnosis of hepatocellular carcinoma in all patients (%)

Factors	Sensitivity	Specificity	PPV	NPV	Accuracy
MnSOD (≥ 110 ng/mL)	26.7	97.1	88.9	60.0	64.1
AFP (≥ 40 ng/mL)	33.3	97.1	90.9	62.3	67.2
Combination1	46.7	94.1	87.5	66.7	71.9

¹MnSOD ≥ 110 ng/mL and/or AFP ≥ 40 ng/mL. PPV: Positive predictive value; NPV: Negative predictive value; MnSOD: Manganese superoxide dismutase; AFP: α-fetoprotein.

Table 3 Correlation between serum manganese superoxide dismutase or thioredoxin levels and laboratory data in the hepatocellular carcinoma group

Factors	HCC group (n = 30)
	Serum MnSOD levels		Serum TRX levels
	Correlation coefficient	P value	Correlation coefficient	P value
Age (yr)	-0.97	0.61	0.11	0.55
Plt (× 104/μL)	0.03	0.89	0.66	< 0.001
PT (%)	-0.36	0.05	0.12	0.53
Alb (g/dL)	-0.63	< 0.001	0.19	0.33
T-Bil (mg/dL)	0.25	0.18	0.05	0.79
ALT (IU/L)	0.12	0.52	0.15	0.42
γ-GTP (IU/L)	0.30	0.11	0.28	0.13
AFP (ng/mL)	0.38	0.04	0.11	0.57
DCP (mAU/mL)	0.57	0.001	0.12	0.52

P values were assessed by Spearman’s rank correlation analysis. MnSOD: Manganese superoxide dismutase; TRX: Thioredoxin; HCC: Hepatocellular carcinoma; Plt: Platelet count; PT: Prothrombin time; Alb: Albumin; T-Bil: Total bilirubin; ALT: Alanine aminotransferase; γ-GTP: γ-glutamyl transpeptidase; AFP: α-fetoprotein; DCP: des-γ-carboxy prothrombin.

Table 4 Univariate analysis of prognostic factors in the hepatocellular carcinoma group

Factors	Category	Number	P value1
Single marker
MnSOD (ng/mL)	< 110/≥ 110	22/8	0.01
TRX (ng/mL)	< 80/≥ 80	24/6	0.05
Age (yr)	< 70/≥ 70	12/18	0.23
Plt (× 104/μL)	< 10/≥ 10	19/11	0.38
PT (%)	< 80/≥ 80	15/15	0.02
Alb (g/dL)	< 3.5/≥ 3.5	15/15	0.02
T-Bil (mg/dL)	< 1.5/≥ 1.5	18/12	0.34
ALT (IU/L)	< 40/≥ 40	11/19	0.58
γ-GTP (IU/L)	< 50/≥ 50	17/13	0.98
AFP (ng/mL)	< 40/≥ 40	20/10	<0.01
DCP (mAU/mL)	< 40/≥ 40	16/14	0.02
Staging system
Child-Pugh stage	A/≥ B	16/14	< 0.01
CLIP score	0-1/≥ 2	22/8	0.01
JIS score	0-1/≥ 2	14/16	0.41

¹P values were assessed using the log-rank test. MnSOD: Manganese superoxide dismutase; TRX: Thioredoxin; Plt: Platelet count; PT: Prothrombin time; Alb: Albumin; T-Bil: Total bilirubin; ALT: Alanine aminotransferase; γ-GTP: γ-glutamyl transpeptidase; AFP: Alpha-fetoprotein; DCP: Serum des-γ-carboxy prothrombin; CLIP: Cancer of the Liver Italian Program; JIS: Japan Integrated Staging.

Table 5 Multivariate analysis of prognostic factors in the hepatocellular carcinoma group

Factors	Risk ratio	95% CI	P value
MnSOD (≥ 110 ng/mL)	4.12	1.22-13.88	0.02
AFP(≥ 40 ng/mL)	6.75	1.70-26.85	< 0.01

95% CI: 95% confidence interval; MnSOD: Manganese superoxide dismutase; AFP: α-fetoprotein.