[How to predict the relapse after surgery or radiofrequency of liver metastases of colorectal cancer? Interest of the serum kinetic variation of a matrix metalloproteinase cluster]

Bull Cancer. 2018 Oct;105(10):884-895. doi: 10.1016/j.bulcan.2018.07.007. Epub 2018 Sep 20.
[Article in French]

Abstract

Introduction: Recurrence after liver surgery or radiofrequency is a clinical and biological challenge because it worsens the colorectal cancer prognosis. To date, no biomarker is yet validated to predict the recurrence in order to intensify adjuvant therapy for patients with higher risk. Matrix metalloproteinases play a major role in the metastasis dissemination and tumoral microenvironment and could be a potential biomarker of interest.

Methods: Forty-four patients with liver metastasis treated by surgery or radiofrequency were enrolled in this study. Serum levels of MMP-1, MMP-2, MMP-7, MMP-9 and TIMP-1 were monitored in Elisa after therapy and correlated to the recurrence from January 2004 to December 2007. After the curative treatment, patients were assessed for the recurence for two years by CT-scan and examination.

Results: Post-operative serum level of MMP-9 was significantly higher between J0, J1 and J45 after liver surgery or radiofrequency (***P≤0.001). Level of MMP-2 was significantly increased at M3 and M6 (***P≤0.001) but does not appear to be a risk factor of liver recurrence. The level of TIMP-1 at J0 is a deleterious factor (HR=1.76, P=0.042*).

Conclusion: This is the first study wich correlates the post-operative level of 4 MMPs and TIMP-1 with the risk of liver recurrence after surgery or radiofrequency. Serum TIMP-1 level at J0 could be helpful to identify patients with higher risk but these results need to be confirmed in a large-scale study.

Keywords: Cancer colorectal; Colorectal cancer; Elisa; Liver metastasis; Matrix metalloproteases; Métalloprotéïnases; Métastases hépatiques; TIMPs.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / blood
  • Catheter Ablation
  • Clinical Enzyme Tests
  • Colorectal Neoplasms / pathology*
  • Female
  • Humans
  • Liver Neoplasms / diagnosis*
  • Liver Neoplasms / secondary*
  • Liver Neoplasms / surgery
  • Male
  • Matrix Metalloproteinase 1 / blood*
  • Matrix Metalloproteinase 7 / blood*
  • Matrix Metalloproteinase 9 / blood*
  • Middle Aged
  • Neoplasm Recurrence, Local / blood
  • Neoplasm Recurrence, Local / diagnosis*
  • Time Factors
  • Tissue Inhibitor of Metalloproteinase-1 / blood*
  • Tissue Inhibitor of Metalloproteinase-2 / blood*

Substances

  • Biomarkers, Tumor
  • TIMP1 protein, human
  • TIMP2 protein, human
  • Tissue Inhibitor of Metalloproteinase-1
  • Tissue Inhibitor of Metalloproteinase-2
  • MMP7 protein, human
  • Matrix Metalloproteinase 7
  • MMP9 protein, human
  • Matrix Metalloproteinase 9
  • MMP1 protein, human
  • Matrix Metalloproteinase 1