Yamamoto H, Itoh F, Adachi Y, Fukushima H, Itoh H, Sasaki S, Hinoda Y, Imai K
Department of Internal Medicine, Sapporo Medical University, Japan.
Jpn J Clin Oncol. 1999 Feb;29(2):58-62. doi: 10.1093/jjco/29.2.58.
The prognosis of patients with hepatocellular carcinoma is relatively poor because of the high rate of intrahepatic recurrences. We have previously demonstrated an association between enhanced secretion of active matrix metalloproteinases (MMPs; gelatinase A and matrilysin) and early recurrence in hepatocellular carcinoma. The aim of this study was to examine further the relationship between messenger RNA levels of metalloproteinases and their inhibitors and behavior of this carcinoma.
Messenger RNA expression of gelatinase A, gelatinase B, matrilysin and tissue inhibitor of metalloproteinases (TIMP)-1 and TIMP-2 were analyzed in 30 patients with hepatocellular carcinoma by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). The results were contrasted with the clinicopathological data of the patients.
Enhanced mRNA expression of gelatinase A, gelatinase B and matrilysin in tumor was observed in 20, 22 and 19 of 30 patients, respectively. Enhanced mRNA expression of gelatinase A or gelatinase B and of matrilysin showed trends toward presence of capsular invasion (P = 0.078) and intrahepatic metastasis (P = 0.064), respectively. Concomitant overexpression of gelatinase A and matrilysin was associated with portal invasion, intrahepatic metastasis and recurrence within the first postoperative year (P < 0.05). A modest increase of mRNA expression of TIMP-1 and TIMP-2 in tumor was observed in half of the patients, but did not correlate with any clinicopathological features.
Our results suggest that semiquantitative RT-PCR analysis of MMPs may be helpful in disease management of patients with hepatocellular carcinoma.
由于肝细胞癌肝内复发率高，其患者预后相对较差。我们之前已经证明，活性基质金属蛋白酶（MMPs；明胶酶A和基质溶素）分泌增强与肝细胞癌早期复发之间存在关联。本研究的目的是进一步探讨金属蛋白酶及其抑制剂的信使核糖核酸水平与该癌症生物学行为之间的关系。
采用半定量逆转录聚合酶链反应（RT-PCR）分析30例肝细胞癌患者肿瘤组织中明胶酶A、明胶酶B、基质溶素以及金属蛋白酶组织抑制剂（TIMP）-1和TIMP-2的信使核糖核酸表达情况。将结果与患者的临床病理数据进行对比。
30例患者中，分别有20例、22例和19例肿瘤组织中明胶酶A、明胶酶B和基质溶素的信使核糖核酸表达增强。明胶酶A或明胶酶B以及基质溶素信使核糖核酸表达增强分别显示出有包膜侵犯（P = 0.078）和肝内转移（P = 0.064）的趋势。明胶酶A和基质溶素同时过度表达与门静脉侵犯、肝内转移以及术后第一年复发相关（P < 0.05）。半数患者肿瘤组织中TIMP-1和TIMP-2的信使核糖核酸表达有适度增加，但与任何临床病理特征均无相关性。
我们的结果表明，对MMPs进行半定量RT-PCR分析可能有助于肝细胞癌患者的疾病管理。
