Kuvaja Paula, Talvensaari-Mattila Anne, Turpeenniemi-Hujanen Taina
Department of Oncology and Radiotherapy, Oulu University Hospital, Oulu, Finland.
Int J Cancer. 2008 Aug 15;123(4):846-51. doi: 10.1002/ijc.23531.
TIMP-1 is a natural inhibitor of extracellular matrix degrading enzymes called matrix metalloproteinases. In addition to its capacity to inhibit matrix degradation, TIMP-1 has been shown to promote cell growth and inhibit apoptosis. The expression of TIMP-1 in tumor tissue, as well as in circulating blood, has therefore been shown to associate with worsened survival in several malignancies. In our study, a prospective series of 213 patients with primary breast carcinoma was assessed. Circulating pre- and postoperative TIMP-1 levels were assayed using enzyme-linked immunosorbent assay analysis. It was shown that high preoperative plasma TIMP-1 was a powerful predictor of systemic early relapse in breast carcinoma, with HR 8.1 (95% CI 1.8-37.6) (p = 0.007) as a log-transformed continuous variable in Cox regression univariate analysis. It was shown to be independent of, and superior to, nodal status as a prognostic variable in multivariate analysis, and not associated with any known prognostic clinicopathological parameters. Kaplan-Meier analysis showed that the patients belonging to the highest quartile of circulating TIMP-1 levels had a worsened recurrence-free survival of 79% compared to 94% RFS among patients in the lower quartiles (p = 0.016). The postoperative levels of circulating plasma TIMP-1 were not found to be prognostic for relapse. In conclusion, preoperative plasma TIMP-1 was found to be a powerful prognostic factor for early systemic relapse in primary breast carcinoma.
基质金属蛋白酶组织抑制因子-1（TIMP-1）是细胞外基质降解酶（即基质金属蛋白酶）的天然抑制剂。除了具有抑制基质降解的能力外，TIMP-1还被证明可促进细胞生长并抑制细胞凋亡。因此，TIMP-1在肿瘤组织以及循环血液中的表达已被证明与多种恶性肿瘤患者的生存率降低有关。在我们的研究中，对213例原发性乳腺癌患者进行了前瞻性评估。采用酶联免疫吸附测定分析法检测术前和术后循环血中TIMP-1水平。结果显示，术前血浆TIMP-1水平高是乳腺癌早期全身复发的有力预测指标，在Cox回归单因素分析中，作为对数转换后的连续变量，风险比（HR）为8.1（95%置信区间1.8 - 37.6）（p = 0.007）。在多因素分析中，它被证明是一个独立于淋巴结状态且优于淋巴结状态的预后变量，并且与任何已知的预后临床病理参数均无关联。Kaplan-Meier分析显示，循环血中TIMP-1水平处于最高四分位数的患者无复发生存率为79%，而处于较低四分位数的患者无复发生存率为94%（p = 0.016）。未发现术后循环血浆TIMP-1水平对复发具有预后价值。总之，术前血浆TIMP-1是原发性乳腺癌早期全身复发的有力预后因素。
