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基质金属蛋白酶2和基质金属蛋白酶2组织抑制剂在结直肠腺瘤和癌症患者诊断中的应用

Matrix metalloproteinase 2 and tissue inhibitor of matrix metalloproteinases 2 in the diagnosis of colorectal adenoma and cancer patients.

作者信息

Groblewska Magdalena, Mroczko Barbara, Gryko Mariusz, Kędra Bogusław, Szmitkowski Maciej

机构信息

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

出版信息

Folia Histochem Cytobiol. 2010 Dec;48(4):564-71. doi: 10.2478/v10042-010-0076-1.

Abstract

The aim of the study was to assess the importance of the measurement of matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of matrix metalloproteinases 2 (TIMP-2) in patients with colorectal cancer (CRC) in relation to clinicopathological features of tumor and patients' survival. Additionally, we determined serum MMP-2 and TIMP-2 in colorectal adenoma (CA) patients and healthy controls and compared them with tumor markers, CEA and CA 19-9. The serum levels of MMP-2 and TIMP-2 in 91 CRC patients, 28 CA subjects and 91 healthy controls were determined by ELISA method, but concentrations of CEA and CA 19-9 using MEIA method. Nonparametric statistical analyses were used. Serum levels of MMP-2 and TIMP-2 were significantly lower in CRC patients than in healthy subjects and decreased with tumor stage. Additionally, MMP-2 concentrations were significantly lower in patients with CRC than in CA group. Diagnostic sensitivity of TIMP-2 (59%) was the highest among biomarkers tested and increased in combined use with CEA (79%). Moreover, the area under ROC curve (AUC) of TIMP-2 was larger than AUC of MMP-2 in differentiation between CRC and healthy subjects, but lower than AUC of matrix metalloproteinase 2 in differentiation between colorectal cancer and adenoma. Our findings suggest clinical usefulness of TIMP-2 as a biomarker in the diagnosis of CRC, especially in combination with CEA. However, further investigation is necessary.

摘要

本研究的目的是评估在结直肠癌(CRC)患者中测量基质金属蛋白酶2(MMP - 2)和基质金属蛋白酶组织抑制剂2(TIMP - 2)对于肿瘤临床病理特征及患者生存的重要性。此外,我们测定了大肠腺瘤(CA)患者和健康对照者的血清MMP - 2和TIMP - 2,并将其与肿瘤标志物癌胚抗原(CEA)和糖类抗原19 - 9(CA 19 - 9)进行比较。采用酶联免疫吸附测定(ELISA)法测定91例CRC患者、28例CA患者和91例健康对照者的血清MMP - 2和TIMP - 2水平,采用微粒子酶免疫分析(MEIA)法测定CEA和CA 19 - 9浓度。使用非参数统计分析方法。CRC患者血清MMP - 2和TIMP - 2水平显著低于健康受试者,且随肿瘤分期降低。此外,CRC患者的MMP - 2浓度显著低于CA组。在所检测的生物标志物中,TIMP - 2的诊断敏感性最高(59%),与CEA联合使用时增加(79%)。此外,在区分CRC与健康受试者时,TIMP - 2的ROC曲线下面积(AUC)大于MMP - 2的AUC,但在区分结直肠癌与腺瘤时低于基质金属蛋白酶2的AUC。我们的研究结果表明TIMP - 2作为CRC诊断的生物标志物具有临床实用性,尤其是与CEA联合使用时。然而,仍需进一步研究。

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