Groblewska Magdalena, Mroczko Barbara, Gryko Mariusz, Kędra Bogusław, Szmitkowski Maciej
Department of Biochemical Diagnostics, Medical University, Białystok, Poland.
Folia Histochem Cytobiol. 2010 Dec;48(4):564-71. doi: 10.2478/v10042-010-0076-1.
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.
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。