Fuksiewicz Malgorzata, Kotowicz Beata, Rutkowski Andrzej, Kowalska Maria
Laboratory of Tumor Markers, Department of Pathology and Laboratory Diagnostics, Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Roentgena 5, 02-781, Warsaw, Poland,
Tumour Biol. 2015 May;36(5):3629-35. doi: 10.1007/s13277-014-3000-z. Epub 2014 Dec 31.
The aim of this study was the evaluation of clinical usage of metalloproteinase (MMP): proMMP-1, MMP-2, MMP-7, MMP-9, tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2 in serum of patients with rectal cancer, as well as the selection of parameters of the greatest diagnostic sensitivity and the determination of their relation with clinicopathological features, what is more, the demonstration whether their concentrations may have a prognostic value in the assessment of disease-free survival (DFS) and overall survival (OS). The study comprised 100 patients with rectal cancer including 29 women and 71 men. The tested group was comprised of qualified patients without distant metastasis (M0). It was demonstrated that in patients with rectal cancer, the concentrations of MMP-9, MMP-7, and proMMP-1 as well as TIMP-1 were significantly higher in comparison to the reference group. On the basis of ROC curves, the greatest diagnostic sensitivity of MMP-9 was demonstrated. When evaluating the correlation of tested parameters with the size of the tumor (T1-T2 vs T3-T4), essential differences were shown for proMMP-1 concentrations. The highest percentage of patients with progression had an increased concentration of MMP-7 and TIMP-1. During a 5-year follow-up, univariate log-rank analysis had shown an essential dependence between the concentration of MMP-7 in men and DSF which was confirmed in Cox multivariate analysis. It was demonstrated that the pretreatment concentration of proMMP-1 may be clinically useful when evaluating the mass of the tumor, whereas MMP-7 may be a prognostic factor for DFS in men with rectal cancer without distant metastasis.
本研究的目的是评估金属蛋白酶（MMP）：前MMP-1、MMP-2、MMP-7、MMP-9、金属蛋白酶组织抑制剂（TIMP）-1和TIMP-2在直肠癌患者血清中的临床应用情况，以及选择具有最大诊断敏感性的参数并确定其与临床病理特征的关系，此外，还要证明它们的浓度在评估无病生存期（DFS）和总生存期（OS）时是否具有预后价值。该研究纳入了100例直肠癌患者，其中包括29名女性和71名男性。测试组由无远处转移（M0）的合格患者组成。结果表明，与参照组相比，直肠癌患者血清中MMP-9、MMP-7、前MMP-1以及TIMP-1的浓度显著更高。基于ROC曲线，证实MMP-9具有最大的诊断敏感性。在评估测试参数与肿瘤大小（T1-T2与T3-T4）的相关性时，发现前MMP-1浓度存在显著差异。疾病进展患者中MMP-7和TIMP-1浓度升高的比例最高。在5年的随访期间，单变量对数秩分析显示男性患者中MMP-7浓度与DFS之间存在显著相关性，这在Cox多变量分析中得到了证实。结果表明，在评估肿瘤大小方面，前MMP-1的预处理浓度可能具有临床应用价值，而MMP-7可能是无远处转移的男性直肠癌患者DFS的一个预后因素。
