Wang Chia-Siu, Wu Tsu-Lan, Tsao Kuo-Chien, Sun Chien-Feng
Dept of Pathology, Chang Gung Memorial Hospital, Linkou Medical Center, 5 Fu-Hsing Street, Kwei-Shan, Taoyuan, Taiwan.
Ann Clin Lab Sci. 2006 Winter;36(1):23-30.
Tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) is over-expressed in many human malignancies, including gastric cancer, and is associated with poor outcome. The purpose of this study was to evaluate the clinical and prognostic significance of preoperative serum TIMP-1 levels in gastric cancer patients. One hundred and seventy gastric cancer patients who underwent gastrectomy between 1996 and 2001 were enrolled in this study. The serum concentration of TIMP-1 protein in these patients and in 116 healthy controls was determined using an enzyme-linked immunoassay (ELISA). When a serum TIMP-1 level >95 percentile of healthy controls was set as the upper cut-off value (348.8 ng/ml), abnormally high serum TIMP-1 were observed in 29 (17.1%) of the gastric cancer patients vs 4.3% of healthy controls (p<0.001). The sensitivity and specificity of serum TIMP-1 as a diagnostic tumor marker were 17.1% and 97.7%, respectively. Serum TIMP-1 was positively associated with morphologic appearance (Borrmann type), tumor size, depth of wall invasion, lymph node metastasis, liver metastasis, and peritoneal seeding. It was also positively associated with lymphatic invasion, perineural invasion, and pathological stage. It was not significantly associated with age, gender, tumor location, or histological type. A higher serum TIMP-1 group was significantly associated with lower survival rates than the lower serum TIMP-1 group (cut-off value at the median; 5-yr survival rate: 32.3% vs 55.6%, log-rank p = 0.0011). When the patients were divided into 2 groups using the 95 percentile TIMP-1 level of controls as the cut-off value, 5-yr survival rates were 24.6% and 47.5% respectively for the higher and lower TIMP-1 groups (log rank p = 0.0147). An elevated preoperative level of serum TIMP-1 was significantly associated with progressive disease, advanced stage, and worse survival in gastric cancer patients. Although it is not a good marker for diagnosis, elevated serum TIMP-1 level shows promise as a marker for prognosis in patients with gastric cancer.
基质金属蛋白酶-1组织抑制剂（TIMP-1）在包括胃癌在内的多种人类恶性肿瘤中过度表达，并与不良预后相关。本研究的目的是评估胃癌患者术前血清TIMP-1水平的临床及预后意义。本研究纳入了1996年至2001年间接受胃切除术的170例胃癌患者。采用酶联免疫吸附测定（ELISA）法测定这些患者及116例健康对照者血清中TIMP-1蛋白的浓度。当将血清TIMP-1水平>健康对照者第95百分位数设定为上限临界值（348.8 ng/ml）时，29例（17.1%）胃癌患者血清TIMP-1异常升高，而健康对照者中这一比例为4.3%（p<0.001）。血清TIMP-1作为诊断性肿瘤标志物的敏感性和特异性分别为17.1%和97.7%。血清TIMP-1与形态学表现（Borrmann分型）、肿瘤大小、壁浸润深度、淋巴结转移、肝转移及腹膜种植呈正相关。它还与淋巴管浸润、神经周围浸润及病理分期呈正相关。它与年龄、性别、肿瘤位置或组织学类型无显著相关性。血清TIMP-1水平较高组的生存率显著低于血清TIMP-1水平较低组（以中位数为临界值；5年生存率：32.3%对55.6%，对数秩检验p = 0.0011）。当以对照者TIMP-1水平的第95百分位数作为临界值将患者分为两组时，TIMP-1水平较高组和较低组的5年生存率分别为24.6%和47.5%（对数秩检验p = 0.0147）。术前血清TIMP-1水平升高与胃癌患者疾病进展、分期较晚及预后较差显著相关。虽然它不是一个好的诊断标志物，但血清TIMP-1水平升高有望作为胃癌患者预后的标志物。
