Circulating Cell-Free DNA and Systemic Inflammatory Response after Self-Expandable Metal Stent for Malignant Bowel Obstruction
Author(s): Malene Broholm, Rasmus Bojesen, Mikail Gögenur, Andreas Weinberger Rosen, Sara Watt, Mustafa Bulut, Rasmus Vogelsang, Henning Quist Jensen, Adile Orhan, Ellen Bjerrum, Christina Søs Auður Andersen, Niels Pallisgaard, Thomas Litman, Jesper T Troelsen, Ismail Gögenur
Purpose: A colonic stent as a bridge to elective surgery can improve short-term clinical outcomes. However, the placement of a stent may induce adverse effects on the immune system through the upregulation of proteins associated with migration, angiogenesis, and inflammation, which may affect the long-term oncological outcome. This study aimed to investigate systemic alterations in the systemic inflammatory response and circulating cell-free DNA in relation to stent placement.
Methods: This prospective observational study included 20 patients with acute malignant colonic obstruction. Blood samples were collected at baseline and 1, 4, and 24 hours after stent placement. Protein quantification was performed using a standardized proteomics panel, and baseline samples were compared with samples collected 24 hours after stent placement. Quantitative analysis of circulating cell-free DNA was evaluated at baseline and 1, 4, and 24 hours after stent placement.
Results: We identified 11 significantly changed protein concentrations (ARG1, GZMA, PGF, GZMH, KLRD1, CCL23, IL5, CCL19, PTN, MUC-16, CD8A) and a tendency towards higher concentration in three proteins (CAIX, CXCL1, IL6) in the 24h samples compared to baseline. Among the proteins mentioned, eight have been associated with tumor-promoting functions, such as proliferation, migration, and angiogenesis. Additionally, two proteins (CD8A and CCL19) are associated with anti-tumor effects. Quantitative analysis of circulating cell-free DNA did not reveal any significant differences between baseline, 1, 4, and 24 hours after stent placement.
Conclusions: Stent placement may induce a systemic inflammatory response potentially associated with tumor-promoting functions. However, we did not find an increase in systemic cell-free DNA. This study supports the importance of further investigating to determine systemic effects in relation to stent placement and potentially identify future targets for medical treatment in addition to the procedure.