High expression of secretory leukocyte protease inhibitor (SLPI) in stage III micro-satellite stable colorectal cancer is associated with reduced disease recurrence

Sandrine Nugteren, Sjoerd H. den Uil, Pien M. Delis-van Diemen, Ytje Simons-Oosterhuis, Dicky J. Lindenbergh-Kortleve, Daniëlle H. van Haaften, Hein B.A.C. Stockmann, Joyce Sanders, Gerrit A. Meijer, Remond J.A. Fijneman, Janneke N. Samsom*

*Corresponding author for this work

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Abstract

Secretory leukocyte protease inhibitor (SLPI) is a pleiotropic protein produced by healthy intestinal epithelial cells. SLPI regulates NF-κB activation, inhibits neutrophil proteases and has broad antimicrobial activity. Recently, increased SLPI expression was found in various types of carcinomas and was suggested to increase their metastatic potential. Indeed, we demonstrated that SLPI protein expression in colorectal cancer (CRC) liver metastases and matched primary tumors is associated with worse outcome, suggesting that SLPI promotes metastasis in human CRC. However, whether SLPI plays a role in CRC before distant metastases have formed is unclear. Therefore, we examined whether SLPI expression is associated with prognosis in CRC patients with localized disease. Using a cohort of 226 stage II and 160 stage III CRC patients we demonstrate that high SLPI protein expression is associated with reduced disease recurrence in patients with stage III micro-satellite stable tumors treated with adjuvant chemotherapy, independently of established clinical risk factors (hazard rate ratio 0.54, P-value 0.03). SLPI protein expression was not associated with disease-free survival in stage II CRC patients. Our data suggest that the role of SLPI in CRC may be different depending on the stage of disease. In stage III CRC, SLPI expression may be unfavorable for tumors, whereas SLPI expression may be beneficial for tumors once distant metastases have established.

Original languageEnglish
Article number12174
JournalScientific Reports
Volume12
Issue number1
DOIs
Publication statusPublished - 16 Jul 2022

Bibliographical note

Funding Information:
SN was funded by the Dutch Digestive Foundation (grant registration number: Focus Project 15–17; https://www.mlds.nl ). JNS received the grant. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Publisher Copyright: © 2022, The Author(s).

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