Abstract
BackgroundMatrix metalloproteinase-8 (MMP-8) is a protease mainly expressed by neutrophils that cleaves numerous substrates, including collagens and cytokines. We have previously shown that serum MMP-8 levels increase in colorectal cancer (CRC) and correlate with distant metastasis. However, short follow-up in our prospective cohort did not enable survival analyses at the time of the first publication.MethodsPreoperative serum MMP-8 levels were measured by immunofluorometric assay in 271 CRC patients and related to clinicopathological parameters, markers of systemic inflammation (modified Glasgow Prognostic Score, mGPS; serum levels of C-reactive protein (CRP), albumin and 13 cytokines), the density of six types of tumour-infiltrating immune cells and survival.ResultsIncreased MMP-8 levels associated with higher mGPS and higher serum levels of CRP and several cytokines, including IL-1ra, IL-7 and IL-8 (p < 0.001 for all). Serum MMP-8 negatively correlated with tumour-infiltrating mast cells (invasive margin: p = 0.005, tumour centre: p = 0.010). The patients with high-serum MMP-8 levels (>100 ng/mL) had poor cancer-specific survival, independent of tumour stage, grade, lymphatic invasion, patient age, BRAF VE1 immunohistochemistry, mismatch repair deficiency, Immunoscore and mGPS (multivariate HR 2.12, 95% CI 1.21–3.71, p = 0.009).ConclusionsHigh-serum MMP-8 levels are associated with systemic inflammation and adverse outcome in CRC.
Highlights
Matrix metalloproteinase-8 (MMP-8) is an endopeptidase mainly produced by neutrophils, but it is expressed at low levels by a variety of other inflammatory, epithelial and stromal cells.[1]
The main findings of the present study indicate that high-serum MMP-8 levels are associated with adverse cancer-specific survival (CSS) in colorectal cancer (CRC) independent of other prognostic parameters, including TNM stage, grade, lymphatic invasion, BRAF VE1 immunohistochemistry, MMR deficiency, Immunoscore and modified Glasgow Prognostic Score (mGPS)
Strong positive correlations were detected between serum MMP-8 and serum levels of C-reactive protein (CRP) and several cytokines, including IL-1ra, IL-7 and IL-8, indicating that serum MMP-8 levels are associated with systemic inflammation in CRC
Summary
Matrix metalloproteinase-8 (MMP-8) is an endopeptidase mainly produced by neutrophils, but it is expressed at low levels by a variety of other inflammatory, epithelial and stromal cells.[1]. We have previously shown that serum MMP-8 levels increase in colorectal cancer (CRC) and correlate with distant metastasis. METHODS: Preoperative serum MMP-8 levels were measured by immunofluorometric assay in 271 CRC patients and related to clinicopathological parameters, markers of systemic inflammation (modified Glasgow Prognostic Score, mGPS; serum levels of C-reactive protein (CRP), albumin and 13 cytokines), the density of six types of tumour-infiltrating immune cells and survival. RESULTS: Increased MMP-8 levels associated with higher mGPS and higher serum levels of CRP and several cytokines, including IL-1ra, IL-7 and IL-8 (p < 0.001 for all). The patients with high-serum MMP-8 levels (>100 ng/mL) had poor cancer-specific survival, independent of tumour stage, grade, lymphatic invasion, patient age, BRAF VE1 immunohistochemistry, mismatch repair deficiency, Immunoscore and mGPS (multivariate HR 2.12, 95% CI 1.21–3.71, p = 0.009). CONCLUSIONS: High-serum MMP-8 levels are associated with systemic inflammation and adverse outcome in CRC
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