Peritoneal infection after colorectal cancer surgery induces substantial alterations in postoperative protein levels: an exploratory study

Abstract

Purpose: Peritoneal infection, due to anastomotic leakage, after resection for colorectal cancer have been shown to associate with increased cancer recurrence and mortality, as well as cardiovascsular morbidity. Alterations in circulating protein levels could help shed light on the underlying mechanisms, prompting this exploratory study of 64 patients operated for colorectal cancer with anastomosis.

Methods: Thirty-two cases who suffered a postoperative peritoneal infection were matched with 32 controls who had a complication-free postoperative stay. Proteins in serum samples at their first postoperative visit and at one year after surgery were analysed using proximity extension assays and enzyme-linked immunosorbent assays. Multivariate projection methods, adjusted for multiple testing, were used to compare levels between groups, and enrichment and network analyses were performed.

Results: Seventy-seven proteins, out of 270 tested, were differentially expressed at a median sampling time of 41 days postoperatively. These proteins were all normalised one year after surgery. Many of the differentially expressed top hub proteins have known involvement in cancer progression, survival, invasiveness and metastasis. Over-represented pathways were related to cardiomyopathy, cell-adhesion, extracellular matrix, phosphatidylinositol-3-kinase/Akt (PI3K-Akt) and transforming growth factor beta (TGF-β) signaling.

Conclusion: These affected proteins and pathways could provide clues as to why patients with peritoneal infection might suffer increased cancer recurrence, mortality and cardiovascular morbidity.

Keywords: Anastomotic leakage; Colorectal cancer; Inflammation; Pathways; Proteomics; Recurrence; Survival.

Fig. 1

Volcano plot of evaluated proteins Differentially expressed in green (upregulated) or yellow (downregulated). One non-significant differentially expressed protein with a fold change mean of approximately 4.5 was removed from the plot to increase readability

Fig. 2

Hub proteins of differentially expressed serum proteins Top 10 ranked hub proteins were derived from differentially expressed proteins using MCC method in the CytoScape plugin cytohubba. A stronger shade of red represents a higher interconnected protein. Hub proteins are ranked in the table