Determination and clinical significance of plasma matrix metalloproteinase in patients with hepatocellular carcinoma

Objective To investigate the expression of matrix metalloproteinases ( MMPs) in patients with hepatocellular carcinoma ( HCC) and its association with clinicopathological features. Methods A total of 131 patients who were hospitalized and treated in Beijing YouAn hospital from October 2015 to May 2018 were enrolled, and among these patients, 35 had hepatitis B cirrhosis and 96 had HCC. A total of20 healthy controls who underwent physical examination at the outpatient service during the same period of time were enrolled as healthy control group. Suspension phase chip technology was used to measure the plasma levels of MMP-1, MMP-2, MMP-7, MMP-9, and MMP-10 before treatment. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups, and the Kruskal-Wallis H test was used for comparison between three groups; the Spearman correlation analysis was performed to investigate correlation. Results The HCC group had a plasma level of MMP-1 of 8134. 84 ( 6147. 94-11 148. 47) pg/ml and a plasma level of MMP-7 of 6541. 58 ( 3906. 63-9033. 12) pg/ml, which were significantly higher than the plasma levels of MMP-1 and MMP-7 in the hepatitis B cirrhosis group and the healthy control group ( χ2= 23. 521 and 66. 112, both P < 0. 001) . The HCC group had a plasma level of MMP-2 of 103 774. 45 ( 90 485. 91-123 673. 90) pg/ml, which was significantly higher than that in the healthy control group ( P< 0. 05) . The patients with a tumor diameter of ≥5 cm, distant metastasis, portal venous invasion, clinical stage Ⅲ/Ⅳ, or Edmondson-Steiner ( ES) grade Ⅲ/Ⅳ had a significantly higher plasma level of MMP-1 than those with a tumor diameter of < 5 cm ( Z =-7. 313, P< 0. 001) , without distant metastasis ( Z =-6. 569, P < 0. 001) , without portal venous invasion ( Z =-6. 051, P < 0. 001) , with clinical stage Ⅰ/Ⅱ ( Z =-5. 844, P < 0. 001) , or with ES grade Ⅰ/Ⅱ ( Z =-7. 423, P < 0. 001) . The patients with distant metastasis, portal venous invasion, clinical stage Ⅲ/Ⅳ, or ES grade Ⅲ/Ⅳ had a significantly higher plasma level of MMP-7 than those without distant metastasis ( Z =-3. 454, P = 0. 001) , without portal venous invasion ( Z =-3. 846, P < 0. 001) , with clinical stage Ⅰ/Ⅱ ( Z =-2. 285, P= 0. 022) , or with ES grade Ⅰ/Ⅱ ( Z =-3. 287, P = 0. 001) . Conclusion The expression of MMP-1 and MMP-7 in HCC patients is associated with HCC metastasis, portal venous invasion, clinical stage, and pathological grade and can help to evaluate the severity and prognosis of tumor invasion in HCC patients.