State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, Cancer Institute Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100021, PR China.
Lung Cancer. 2010 Sep;69(3):341-7. doi: 10.1016/j.lungcan.2009.12.007. Epub 2010 Jan 8.
Matrix metalloproteinase-1 (MMP-1) participates in a variety of physiological and pathological processes. We previously found that MMP-1 was one of the lung cancer-related proteins detectable in peripheral blood. To validate our preliminary observations and explore the clinical significance of MMP-1 for lung cancer further, we carried out the present study. The concentrations of MMP-1 in circulating plasma specimens of 170 lung cancer patients and 70 healthy individuals were measured by an enzyme-linked immunosorbance assay. The expression status of the MMP-1 in archival tissue samples from 122 lung cancer patients was examined by immunohistochemical analysis. The correlation between the MMP-1 levels and prognosis of the lung cancer patients was then assessed statistically. Protein levels of MMP-1 were considerably raised in the plasma from lung cancer patients relative to those in healthy controls. The high plasma MMP-1 levels were associated with advanced-stage of the disease and significantly lower overall survival rate of the patients. Coincidently, MMP-1 protein extraordinarily overexpressed in the tumour tissues of lung cancer; and the up-regulated MMP-1 was associated with the progression (including tumour size, staging and lymphatic invasion), especially with decreased survival rate of the patients. Statistic analysis revealed that MMP-1 protein levels had an independent influence on survival. MMP-1 levels were elevated in both tumour tissue and blood; the latter may serve as an independent predictor for survival of lung cancer patients. MMP-1 protein levels in plasma/serum thus represent a potential and clinically relevant biomarker for the prognosis of patients with lung cancers.
基质金属蛋白酶-1(MMP-1)参与多种生理和病理过程。我们之前发现 MMP-1 是外周血中可检测到的肺癌相关蛋白之一。为了验证我们的初步观察结果,并进一步探讨 MMP-1 对肺癌的临床意义,我们进行了本研究。通过酶联免疫吸附试验测量了 170 例肺癌患者和 70 例健康个体的循环血浆标本中 MMP-1 的浓度。通过免疫组织化学分析检测了 122 例肺癌患者的存档组织样本中 MMP-1 的表达状态。然后通过统计学方法评估了 MMP-1 水平与肺癌患者预后的相关性。与健康对照组相比,肺癌患者血浆中的 MMP-1 蛋白水平明显升高。高血浆 MMP-1 水平与疾病晚期相关,并且患者的总生存率显著降低。巧合的是,MMP-1 蛋白在肺癌肿瘤组织中过度表达;并且上调的 MMP-1 与进展(包括肿瘤大小、分期和淋巴浸润)相关,特别是与患者生存率降低相关。统计分析表明 MMP-1 蛋白水平对生存有独立影响。肿瘤组织和血液中 MMP-1 水平均升高;后者可能是肺癌患者生存的独立预测因子。因此,血浆/血清中的 MMP-1 蛋白水平代表了肺癌患者预后的一个潜在且具有临床相关性的生物标志物。