Prognostic value of serum MMP-8, -9 and TIMP-1 in patients with hepatocellular carcinoma

Figures & data

Table I. Clinical characteristics of patients with hepatocellular carcinoma.

Patients (n)	134
Gender (males/females)	105/29
Age, years (median, range)	68 (16–87)
Cirrhosis	63 (51%)
Child–Pugh class
A	32 (51%)
B	25 (40%)
C	6 (10%)
BCLC class
0	3 (2%)
A	29 (22%)
B	64 (48%)
C	28 (21%)
D	10 (7%)
Tumor size (mean, SD)	7 cm (4)
0–3 cm	19 (14%)
3.1–5 cm	32 (24%)
> 5 cm	83 (62%)
Tumor number
single	93 (69%)
multinodular	41 (31%)
Tumor grade
1	26 (19%)
2	41 (31%)
3	20 (15%)
unknown	47 (34%)
Extrahepatic disease
yes	21 (16%)
no	113 (84%)

BCLC = Barcelona Clinic Liver Cancer.

Table II. Cause of death in HCC patients.

n	111
HCC	83 (75%)
Cirrhosis	8 (7%)
Other	16 (14%)
cardiovascular	10
trauma	2
other malignancy	3
transplantation complication	1
Unknown	4 (4%)

HCC = hepatocellular carcinoma.

Table III. The median serum concentrations and interquartile ranges of MMP-8, MMP-9, TIMP-1, α-fetoprotein, and the molar ratios of MMPs and TIMP-1 in patients with HCC.

	HCC (n = 134)
	Median	IQR
MMP-8 (ng/mL)	6.5	2.6–16
MMP-9 (ng/mL)	31	22–56
TIMP-1 (ng/mL)	209	159–272
MMP-8/TIMP-1	0.014	0.005–0.034
MMP-9/TIMP-1	0.043	0.03–0.078
AFP (kU/L)	8	3–140

AFP = α-fetoprotein; HCC = hepatocellular carcinoma; IQR = interquartile range.

Figure 1. Kaplan–Meier survival curves in patients with HCC. A: Low and high MMP-8 serum concentrations. B: low and high MMP-9 serum concentrations. C: Low and high TIMP-1 serum concentrations. D: Low and high molar ratios of MMP-8/TIMP-1. E: Low and high molar ratios of MMP-9/TIMP-1. F: Low and high AFP serum concentrations.

Table IV. Cox multivariable regression analysis of serum MMPs and clinical parameters in relation to overall survival of HCC patients.

	Multivariable analysis
	HR (95% CI)	P
MMP-8	1.005 (0.999–1.010)	0.087
MMP-9	1.019 (1.005–1.033)	0.008
TIMP-1	1.000 (0.998–1.001)	0.502
MMP-8/TIMP-1 ratio	1.060 (0.022–52.195)	0.977
MMP-9/TIMP-1 ratio	0.0001 (0.0001–0.005)	0.001
MMP-13	0.739 (0.482–1.133)	0.165
AFP	1.000 (1.000–1.000)	0.345
BCLC	1.315 (0.993–1.742)	0.056
Therapy	0.704 (0.597–0.831)	0.0001

BCLC = Barcelona Clinic Liver Cancer score; CI = confidence interval; HR = hazard ratio.

Llovet JM, Burroughs A, Bruix J. Hepatocellular carcinoma. Lancet. 2003;362:1907–17.

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