University of Oulu

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

High-serum MMP-8 levels are associated with decreased survival and systemic inflammation in colorectal cancer

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Author: Sirniö, Päivi1,2; Tuomisto, Anne1,2; Tervahartiala, Taina3;
Organizations: 1Cancer and Translational Medicine Research Unit, University of Oulu
2Oulu University Hospital and Medical Research Center Oulu
3Department of Oral and Maxillofacial Diseases, University of Helsinki
4Research Unit of Surgery, Anesthesia and Intensive Care, University of Oulu
5Research Unit of Biomedicine and Biocenter Oulu, Department of Physiology, University of Oulu
6Department of Gastroenterology and Metabolism, Poznan University of Medical Sciences
7Helsinki University Hospital
Format: article
Version: accepted version
Access: open
Online Access: PDF Full Text (PDF, 1.7 MB)
Persistent link:
Language: English
Published: Springer Nature, 2018
Publish Date: 2018-12-03


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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Series: British journal of cancer
ISSN: 0007-0920
ISSN-E: 1532-1827
ISSN-L: 0007-0920
Volume: 119
Issue: 2
Pages: 213 - 219
DOI: 10.1038/s41416-018-0136-4
Type of Publication: A1 Journal article – refereed
Field of Science: 3122 Cancers
Funding: This work was supported by grants from Finnish Cancer Society, K. Albin Johansson Foundation, and Orion Research Foundation.
Copyright information: © 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: