Serum MMP-8 levels increase in colorectal cancer and correlate with disease course and inflammatory properties of primary tumors

Department of Pathology, Institute of Diagnostics, University of Oulu, Oulu, Finland.
International Journal of Cancer (Impact Factor: 5.09). 08/2012; 131(4):E463-74. DOI: 10.1002/ijc.26435
Source: PubMed


Matrix metalloproteinases (MMPs) form a family of zinc-dependent endoproteases participating in cancer pathogenesis by promoting invasion and regulating growth signaling, apoptosis, angiogenesis and immune responses. MMP-8 is an intriguing MMP with recently discovered antitumor activity and immunoregulatory properties, but its role in colorectal cancer (CRC) has not been studied extensively. Preoperative serum MMP-8 levels (S-MMP-8) of 148 CRC patients and 83 healthy controls were measured using an immunofluorometric assay and related to clinical and pathological parameters. The patients had higher S-MMP-8 than the controls (median 63.0 vs. 17.2 ng/ml, p = 1.5E - 9), and a receiver operating characteristics analysis yielded an area under the curve of 0.751 in differentiating the groups. In univariate analyses, S-MMP-8 correlated positively with disease stage (p = 4.5E - 4), the degree of primary tumor necrosis (p = 0.0024) and blood neutrophil count (Pearson r = 0.523, p = 2.5E - 9). Particular interest was also addressed to the inflammatory properties of the tumors, and both variables studied, peritumoral tumor-destructing inflammatory infiltrate and Crohn's-like lymphoid reaction (CLR), showed a negative correlation with S-MMP-8 (p = 0.041 and p = 0.0057, respectively). In a multiple linear regression analysis, high S-MMP-8 associated with elevated blood neutrophil count, distant metastases, low-grade CLR and low body mass index. Overall, our results indicate that MMP-8 is involved in the course and progression of CRC influencing the immune response against the tumor and contributing to the resolution of necrosis. Serum or plasma MMP-8 may prove to be a worthy biomarker for CRC.

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