High-serum MMP-8 levels are associated with decreased survival and systemic inflammation in colorectal cancer
Sirniö, Päivi; Tuomisto, Anne; Tervahartiala, Taina; Sorsa, Timo; Klintrup, Kai; Karhu, Toni; Herzig, Karl-Heinz; Mäkelä, Jyrki; Karttunen, Tuomo J.; Salo, Tuula; Mäkinen, Markus J.; Väyrynen, Juha P. (2018-05-29)
Sirniö, P., Tuomisto, A., Tervahartiala, T., Sorsa, T., Klintrup, K., Karhu, T., Herzig, K., Mäkelä, J., Karttunen, T., Salo, T., Mäkinen, M., Väyrynen, J. (2018) High-serum MMP-8 levels are associated with decreased survival and systemic inflammation in colorectal cancer. British Journal of Cancer, 119 (2), 213-219. doi:10.1038/s41416-018-0136-4
© 2018 Springer Nature Limited. All rights reserved. This is a post-peer-review, pre-copyedit version of an article published in the British Journal of Cancer. The final authenticated version is available online at: https://doi.org/10.1038/s41416-018-0136-4.
Background: Matrix 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.
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). 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).
Conclusions: High-serum MMP-8 levels are associated with systemic inflammation and adverse outcome in CRC.
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