Circulating MMP2 and MMP9 in breast cancer - Potential role in classification of patients into low risk, high risk, benign disease and breast cancer categories

Stella B. Somiari*, Richard I. Somiari, Caroline M. Heckman, Cara H. Olsen, Rick M. Jordan, Stephen J. Russell, Craig D. Shriver

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

126 Scopus citations

Abstract

Matrix metalloproteinase (MMP) 2 and 9 are involved in cancer invasion and metastasis, and increased levels occur in serum and plasma of breast cancer (BC) patients. It is, however, unclear whether changes in serum levels can be exploited for early detection or classification of patients into different risk/disease categories. In our study, we measured concentration and activity of MMP2/9 in sera of 345 donors classified as low risk (Gail score < 1.7), high risk (HR) (Gail score ≥1.7), benign disease or BC. Kruskal-Wallis and Mann-Whitney nonparametric tests showed that total-MMP2 concentration is higher in HR compared to control (p = 0.012), benign (p = 0.001) and cancer (p = 0.007). Active MMP2 (aMMP2) concentration is higher in control than benign and cancer (p < 0.001, respectively). Total and aMMP9 concentrations are higher in cancer than benign (p < 0.001, p = 0.002, respectively). Total-MMP2 and total-MMP9 activities are lower in control than benign (p < 0.001, p = 0.002, respectively) and cancer (p < 0.001, respectively). Total-MMP2 and MMP9 activities are also higher in cancer than benign (p = 0.004, p < 0.001) and HR (p = 0.008, p = 0.007, respectively). These results were not affected by age or inclusion/exclusion of donors with noninvasive cancer or atypical hyperplasia. Linear discriminant analysis revealed that HR donors are characterized by lower total-MMP2 and higher aMMP2. Overall group classification accuracy was 64.5%. Independent validation based on the leave-one-out cross validation approach gave an overall classification of 63%. Our study provides evidence supporting the potential role of serum MMP2/9 as biomarkers for breast disease classification.

Original languageEnglish
Pages (from-to)1403-1411
Number of pages9
JournalInternational Journal of Cancer
Volume119
Issue number6
DOIs
StatePublished - 15 Sep 2006
Externally publishedYes

Keywords

  • Breast cancer
  • Breast disease
  • Gail model
  • High risk
  • Matrix metalloproteinase 2 and 9
  • Serum profiling

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