Groblewska Magdalena, Mroczko Barbara, Gryko Mariusz, Pryczynicz Anna, Guzińska-Ustymowicz Katarzyna, Kędra Bogusław, Kemona Andrzej, Szmitkowski Maciej
Department of Biochemical Diagnostics, University Hospital, Białystok, Poland.
Tumour Biol. 2014 Apr;35(4):3793-802. doi: 10.1007/s13277-013-1502-8. Epub 2014 Jan 7.
The objective of the study was the assessment of serum levels and tissue expression of matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of matrix metalloproteinases 2 (TIMP-2) in patients with colorectal cancer (CRC). The study included 72 CRC patients and 68 healthy subjects. The serum levels of MMP-2 and TIMP-2 were measured using enzyme-linked immunosorbent assay (ELISA) method, whereas tissue expression of MMP-2 and TIMP-2 in cancer cells, interstitial inflammatory cells, and adjacent normal colorectal mucosa were examined by immunohistochemical staining of tumor samples. The serum levels of MMP-2 and TIMP-2 in cancer patients were significantly lower than those in control group, but the percentage of positive immunoreactivity of these proteins were higher in malignant and inflammatory cells as compared to normal tissue. There was a significant correlation between MMP-2 immunoreactivity in inflammatory cells and the presence of distant metastases and between TIMP-2 expression in inflammatory cells and tumor size, nodal involvement, and distant metastases. Area under receiver operating characteristic (ROC) curve (AUC) for serum MMP-2 was higher than for serum TIMP-2. Moreover, positive tissue expression of MMP-2 was a significant prognostic factor for CRC patients' survival. Our findings suggest that MMP-2 and TIMP-2 might play a role in the process of colorectal cancer invasion and metastasis, but the significance of their interactions with tumor stroma and interstitial inflammatory infiltration in colorectal neoplasia require further elucidation.
本研究的目的是评估结直肠癌（CRC）患者血清中基质金属蛋白酶2（MMP-2）和基质金属蛋白酶组织抑制剂2（TIMP-2）的水平以及组织表达情况。该研究纳入了72例CRC患者和68名健康受试者。采用酶联免疫吸附测定（ELISA）法检测MMP-2和TIMP-2的血清水平，而通过肿瘤样本的免疫组织化学染色检查癌细胞、间质炎性细胞及相邻正常结直肠黏膜中MMP-2和TIMP-2的组织表达。癌症患者血清中MMP-2和TIMP-2的水平显著低于对照组，但与正常组织相比，这些蛋白在恶性细胞和炎性细胞中的免疫反应阳性率更高。炎性细胞中MMP-2免疫反应性与远处转移的存在之间以及炎性细胞中TIMP-2表达与肿瘤大小、淋巴结受累和远处转移之间存在显著相关性。血清MMP-2的受试者工作特征（ROC）曲线下面积（AUC）高于血清TIMP-2。此外，MMP-2的阳性组织表达是CRC患者生存的一个重要预后因素。我们的研究结果表明，MMP-2和TIMP-2可能在结直肠癌侵袭和转移过程中发挥作用，但它们在结直肠肿瘤形成中与肿瘤基质和间质炎性浸润相互作用的意义需要进一步阐明。
