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

Abstract

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.