2nd Department of Surgery, Semmelweis University, Budapest, Hungary.
1st Department of Surgery, Semmelweis University, Budapest, Hungary.
Dig Dis. 2021;39(3):217-224. doi: 10.1159/000511765. Epub 2020 Sep 22.
We and others have previously shown that matrix metalloproteinases (MMPs) play a role in colorectal cancer (CRC) invasion and metastasis. However, the serum changes of various MMPs and their inhibitors (TIMPs) have scarcely been concomitantly investigated in identical blood samples in the normal colon-adenoma-CRC sequence.
The MMP-2, MMP-7, MMP-9, TIMP-1, and TIMP-2 serum antigen concentrations were determined concomitantly in 19 tumor-free control patients, 19 patients with high-risk colorectal adenoma, and 47 patients with CRC by ELISA technique. The analyzed parameters were also investigated in correlation with CRC stages. Statistical analysis with one-way ANOVA and Student's t test was performed. p values <0.05 were considered significant.
Serum antigen levels of MMPs and TIMPs were significantly increased in patients with CRC and adenomas compared to controls (mean values, ng/mL) (MMP-7: 5.88, 4.44, and 2.89, respectively, p = 0.001; MMP-9: 1,075.81, 999.22, and 845.97, respectively, p = 0.01; TIMP-1: 241.80, 205.98, and 166.53, respectively, p = 0.001; TIMP-2: 83.40, 80.30, and 69.62, respectively, p = 0.01). The elevated serum MMP-7, MMP-9, TIMP-1, and TIMP-2 levels significantly correlated with advanced tumor stages (p < 0.05). No statistically significant differences were observed in MMP-2 levels.
We demonstrate that serum antigen concentrations of MMP-7, MMP-9, TIMP-1, and TIMP-2 were significantly increased in patients with CRC and adenomas compared to controls. These results suggest that MMPs and their inhibitors TIMP-1 and TIMP-2 play an important role in CRC invasion; however, they are also activated in premalignant adenomas. Furthermore, MMP-7, MMP-9, TIMP-1, and TIMP-2 may have a potential prognostic impact in CRC.
我们和其他人之前已经表明，基质金属蛋白酶（MMPs）在结直肠癌（CRC）的侵袭和转移中发挥作用。然而，在正常结肠-腺瘤-CRC 序列的相同血液样本中，各种 MMP 和其抑制剂（TIMP）的血清变化很少同时被研究。
通过 ELISA 技术，我们同时测定了 19 例无肿瘤对照患者、19 例高危结直肠腺瘤患者和 47 例 CRC 患者的 MMP-2、MMP-7、MMP-9、TIMP-1 和 TIMP-2 血清抗原浓度。还将分析的参数与 CRC 分期进行了相关性研究。采用单向方差分析和学生 t 检验进行统计分析。p 值<0.05 被认为具有统计学意义。
与对照组相比，CRC 和腺瘤患者的 MMP 和 TIMP 血清抗原水平显著升高（平均值，ng/mL）（MMP-7：分别为 5.88、4.44 和 2.89，p=0.001；MMP-9：分别为 1075.81、999.22 和 845.97，p=0.01；TIMP-1：分别为 241.80、205.98 和 166.53，p=0.001；TIMP-2：分别为 83.40、80.30 和 69.62，p=0.01）。升高的血清 MMP-7、MMP-9、TIMP-1 和 TIMP-2 水平与晚期肿瘤分期显著相关（p<0.05）。MMP-2 水平无统计学差异。
我们证明，与对照组相比，CRC 和腺瘤患者的 MMP-7、MMP-9、TIMP-1 和 TIMP-2 血清抗原浓度显著升高。这些结果表明，MMPs 及其抑制剂 TIMP-1 和 TIMP-2 在 CRC 侵袭中发挥重要作用；然而，它们也在癌前腺瘤中被激活。此外，MMP-7、MMP-9、TIMP-1 和 TIMP-2 在 CRC 中可能具有潜在的预后影响。
