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血清基质金属蛋白酶2(MMP-2)及其组织抑制剂(TIMP-2)水平在胃癌中的临床意义

Clinical significance of serum levels of matrix metalloproteinase 2 (MMP-2) and its tissue inhibitor (TIMP-2) in gastric cancer.

作者信息

Mroczko Barbara, Lukaszewicz-Zając Marta, Gryko Mariusz, Kędra Bogusław, Szmitkowski Maciej

机构信息

Department of Biochemical Diagnostics, Medical University, Bialystok, Poland.

出版信息

Folia Histochem Cytobiol. 2011;49(1):125-31. doi: 10.5603/fhc.2011.0018.

DOI:10.5603/fhc.2011.0018
PMID:21526499
Abstract

Matrix metalloproteinase 2 (MMP-2) is able to degrade type IV collagen, and thus plays a key role in the migration of tumor cells. MMP-2 activity is inhibited by its tissue inhibitor (TIMP-2). The imbalance between MMPs and TIMPs may facilitate progression of cancer cells. The aim of this study was to compare the clinical importance of MMP-2 and TIMP-2 to that of classical tumor markers, namely carcinoembryonic antigen (CEA) and carbohydrate antigen (CA 19-9) in the diagnosis of gastric cancer (GC) by calculating the diagnostic criteria and estimating the levels of MMP-2, TIMP-2, CEA and CA 19-9 in GC patients in relation to clinicopathological features of cancer. We found that serum levels of MMP-2 and TIMP-2 were significantly lower, whereas serum tumor markers were higher, in GC patients than in healthy subjects. Moreover, concentrations of TIMP-2 and CEA correlated with gastric wall infiltration, while CA 19-9 levels correlated with gastric wall infiltration and the presence of nodal metastasis. None of the proteins tested was found to be an independent prognostic factor for GC patients' survival. The percentage of true positive results of TIMP-2 (61%) was higher than those of MMP-2 (54%) and the classical tumor markers CEA (21%) and CA 19-9 (31%). The highest diagnostic sensitivity was observed for the combined use of TIMP-2 with MMP-2 (77%). The results suggest the greater importance of serum MMP-2 and TIMP-2 than of the classical tumor markers CEA and CA 19-9 in the diagnosis of GC. But this issue requires further investigation.

摘要

基质金属蛋白酶2(MMP-2)能够降解IV型胶原,因此在肿瘤细胞迁移中起关键作用。MMP-2的活性受到其组织抑制剂(TIMP-2)的抑制。MMPs与TIMPs之间的失衡可能促进癌细胞的进展。本研究的目的是通过计算诊断标准并评估GC患者中MMP-2、TIMP-2、癌胚抗原(CEA)和糖类抗原(CA 19-9)的水平与癌症临床病理特征的关系,比较MMP-2和TIMP-2与经典肿瘤标志物在胃癌(GC)诊断中的临床重要性。我们发现,GC患者血清中MMP-2和TIMP-2水平显著低于健康受试者,而血清肿瘤标志物水平则较高。此外,TIMP-2和CEA的浓度与胃壁浸润相关,而CA 19-9水平与胃壁浸润和淋巴结转移的存在相关。在所检测的蛋白质中,没有一种被发现是GC患者生存的独立预后因素。TIMP-2的真阳性结果百分比(61%)高于MMP-2(54%)以及经典肿瘤标志物CEA(21%)和CA 19-9(31%)。TIMP-2与MMP-2联合使用时观察到最高的诊断敏感性(77%)。结果表明,血清MMP-2和TIMP-2在GC诊断中比经典肿瘤标志物CEA和CA 19-9更重要。但这个问题需要进一步研究。

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