A1 Refereed original research article in a scientific journal
Systemic inflammatory response in colorectal cancer is associated with tumour mismatch repair and impaired survival
Authors: Hjortborg, Mats; Edin, Sofia; Böckelman, Camilla; Kaprio, Tuomas; Li, Xingru; Gkekas, Ioannis; Hagström, Jaana; Strigard, Karin; Haglund, Caj; Gunnarsson, Ulf; Palmqvist, Richard
Publisher: NATURE PORTFOLIO
Publishing place: BERLIN
Publication year: 2024
Journal: Scientific Reports
Journal name in source: SCIENTIFIC REPORTS
Journal acronym: SCI REP-UK
Article number: 29738
Volume: 14
Issue: 1
Number of pages: 11
ISSN: 2045-2322
eISSN: 2045-2322
DOI: https://doi.org/10.1038/s41598-024-80803-6
Web address : https://www.nature.com/articles/s41598-024-80803-6
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/477205192
The systemic inflammatory response (SIR), defined as elevated levels of circulating C-reactive protein (CRP), is an important predictor of impaired survival in colorectal cancer. The aim of this study was to explore the prognostic role of SIR and its association with tumour mismatch repair status and the immune response. Immune activity profiles of mononuclear cells isolated from CRC tissues and blood in the U-CAN exploration cohort (n = 69), were analysed by flow cytometry. In the U-CAN validation cohort (n = 257), T-helper cells (T-bet(+)), cytotoxic T cells (CD8(+)), regulatory T cells (FoxP3(+)), B cells (CD20(+)), and macrophages (CD68(+)) were analysed by multispectral imaging. Microsatellite instability was determined using five mononucleotide-repeat microsatellite markers. Patients with high CRP levels (> 10 mg/l) were significantly more often diagnosed with high-grade tumours and tumours exhibiting microsatellite instability. However, some patients with high CRP levels were found to have microsatellite-stable tumours. Furthermore, high CRP levels were associated with specific tumour immune traits including an augmented macrophage response and were significantly linked to poorer cancer-specific survival, particularly in patients with microsatellite-stable tumours. In conclusion, our findings suggest an interplay between SIR and mismatch repair status in CRC prognosis which needs to be further explored.
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Funding information in the publication:
Open access funding provided by Umea University. This work was supported by grants from the Swedish Cancer Society, the Swedish Research Council, The Sjoberg Foundation, the Cancer Foundation in Northern Sweden, and a regional agreement between Umea University and Region Vasterbotten (ALF). The funders had no role in study design, data collection, analyses, or interpretation of the data.
