Hayasaka A, Suzuki N, Fujimoto N, Iwama S, Fukuyama E, Kanda Y, Saisho H
First Department of Medicine, Chiba University School of Medicine, Japan.
Hepatology. 1996 Nov;24(5):1058-62. doi: 10.1053/jhep.1996.v24.pm0008903375.
Matrix metalloproteinase 9 (MMP-9), a 92-kd gelatinase/type IV collagenase, has been implicated as playing an important role in cancer invasion and metastasis. A previous study showed that serum type IV collagenase activity correlated with metastasis by hepatocellular carcinoma (HCC). The aims of this study were to determine the plasma levels of immunoreactive MMP-9 in patients with HCC and to compare the levels with the clinical features including vascular invasion.
This study included 100 patients with HCC, 21 patients with chronic hepatitis (CH), 24 patients with liver cirrhosis (LC), and 138 healthy control subjects. Plasma MMP-9 levels were measured with a specific one-step sandwich enzyme immunoassay.
Plasma MMP-9 levels in HCC (62 [33 to 130 ng/mL] median [25%, 75%], 13 to 660 ng/mL, minimum, maximum) were significantly elevated compared with those in normal controls (36 [25 to 45], range, 2.8-70 ng/mL), in CH (28 [18 to 30], 13 to 66 ng/mL) and in LC (35 [26 to 58], 16 to 86 ng/mL) (P < .0000001; P = .0000003; and P = .00205, respectively). When the cut-off level was defined as 60 ng/mL from a receiver operating characteristic curve, plasma MMP-9 concentrations had a sensitivity of 53% and a specificity of 89% for the detection of HCC from CH and LC. The levels were significantly higher in HCC patients with macroscopic portal venous invasion (79 [36 to 160], 15-660 ng/mL) than those without the invasion (44 [27 to 80], 13 to 210 ng/mL) (P = .00726). Plasma MMP-9 levels in patients with HCC were not correlated with tumor number, size, volume, or serum alpha-fetoprotein levels.
The present data suggest that plasma MMP-9 levels can be a candidate for a novel marker for HCC. The levels appear to reflect its potential and ongoing activity of vascular invasion. A long-term follow-up of the patients will be necessary to determine whether increased plasma MMP-9 levels are predictive of more invasive and metastatic HCC.
基质金属蛋白酶9（MMP - 9），一种92kd的明胶酶/IV型胶原酶，被认为在癌症侵袭和转移中起重要作用。先前的一项研究表明，血清IV型胶原酶活性与肝细胞癌（HCC）的转移相关。本研究的目的是测定HCC患者血浆中免疫反应性MMP - 9的水平，并将其与包括血管侵犯在内的临床特征进行比较。
本研究纳入了100例HCC患者、21例慢性肝炎（CH）患者、24例肝硬化（LC）患者以及138名健康对照者。采用特异性一步夹心酶免疫测定法测量血浆MMP - 9水平。
与正常对照者（36[25至45]，范围2.8 - 70ng/mL）、CH患者（28[18至30]，13至66ng/mL）和LC患者（35[26至58]，16至86ng/mL）相比，HCC患者的血浆MMP - 9水平（中位数[25%，75%]为62[范围33至130ng/mL]，最低值13至最高值660ng/mL）显著升高（P <.0000001；P =.0000003；P =.00205）。根据受试者工作特征曲线将临界值定义为60ng/mL时，血浆MMP - 9浓度对从CH和LC中检测出HCC的敏感性为53%，特异性为89%。有肉眼可见门静脉侵犯的HCC患者的MMP - 9水平（79[36至160]，15至660ng/mL）显著高于无侵犯的患者（44[27至80]，13至210ng/mL）（P =.00726）。HCC患者的血浆MMP - 9水平与肿瘤数量、大小、体积或血清甲胎蛋白水平无关。
目前的数据表明，血浆MMP - 9水平可能是HCC一种新的标志物。这些水平似乎反映了其血管侵犯的潜在和持续活性。有必要对患者进行长期随访，以确定血浆MMP - 9水平升高是否可预测更具侵袭性和转移性的HCC。
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