Peripheral blood leucocytes show differential expression of tumour progression‐related genes in colorectal cancer patients who have a postoperative intra‐abdominal infection: a prospective matched cohort study

<jats:title>Abstract</jats:title><jats:sec><jats:title>Aim</jats:title><jats:p>Anastomotic leak is associated with higher rates of recurrence after surgery for colorectal cancer. However, the mechanisms responsible are unknown. We hypothesized that the infection‐induced inflammatory response may induce overexpression of tumour progression‐related genes in immune cells. The aim was to investigate the effect of postoperative intra‐abdominal infection on the gene expression patterns of peripheral blood leucocytes (<jats:styled-content style="fixed-case">PBL</jats:styled-content>) after surgery for colorectal cancer.</jats:p></jats:sec><jats:sec><jats:title>Method</jats:title><jats:p>Prospective matched cohort study. Patients undergoing surgery for colorectal cancer were included. Patients who had anastomotic leak or intra‐abdominal abscess were included in the infection group (<jats:italic>n </jats:italic>=<jats:italic> </jats:italic>23) and matched with patients without complications for the control group (<jats:italic>n </jats:italic>=<jats:italic> </jats:italic>23). <jats:styled-content style="fixed-case">PBL</jats:styled-content> were isolated from postoperative blood samples. Total <jats:styled-content style="fixed-case">RNA</jats:styled-content> was extracted and hybridized to the Affymetrix Human Gene 1.0 <jats:styled-content style="fixed-case">ST</jats:styled-content> microarray.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Patients in the infection group displayed 162 upregulated genes and 146 downregulated genes with respect to the control group. Upregulated genes included examples coding for secreted cytokines involved in tumour growth and invasion (<jats:italic>S100P</jats:italic>,<jats:italic> <jats:styled-content style="fixed-case">HGF</jats:styled-content></jats:italic>,<jats:italic> <jats:styled-content style="fixed-case">MMP</jats:styled-content>8</jats:italic>,<jats:italic> <jats:styled-content style="fixed-case">MMP</jats:styled-content>9</jats:italic>,<jats:italic> <jats:styled-content style="fixed-case">PDGFC</jats:styled-content></jats:italic>,<jats:italic> <jats:styled-content style="fixed-case">IL</jats:styled-content>1R2</jats:italic>). Infection also upregulated some proangiogenic genes (<jats:italic><jats:styled-content style="fixed-case">CEP</jats:styled-content>55</jats:italic>,<jats:italic> <jats:styled-content style="fixed-case">TRPS</jats:styled-content>1</jats:italic>) and downregulated some inhibitors of angiogenesis (<jats:italic><jats:styled-content style="fixed-case">MME</jats:styled-content></jats:italic>,<jats:italic> <jats:styled-content style="fixed-case">ALOX</jats:styled-content>15</jats:italic>,<jats:italic> <jats:styled-content style="fixed-case">CXCL</jats:styled-content>10</jats:italic>). Finally, some inhibitors (<jats:italic><jats:styled-content style="fixed-case">HP</jats:styled-content></jats:italic>,<jats:italic> <jats:styled-content style="fixed-case">ORM</jats:styled-content>1</jats:italic>,<jats:italic> <jats:styled-content style="fixed-case">OLFM</jats:styled-content>4</jats:italic>,<jats:italic> <jats:styled-content style="fixed-case">IRAK</jats:styled-content>3</jats:italic>) and activators (<jats:italic><jats:styled-content style="fixed-case">GNLY</jats:styled-content></jats:italic>,<jats:italic> <jats:styled-content style="fixed-case">PRF</jats:styled-content>1</jats:italic>,<jats:italic> <jats:styled-content style="fixed-case">FGFBP</jats:styled-content>2</jats:italic>) of antitumour immunity were upregulated and downregulated, respectively, suggesting that the inflammatory environment caused by a postoperative infection favours immune evasion mechanisms of the tumour.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Analysis of <jats:styled-content style="fixed-case">PBL</jats:styled-content> shows differential expression of certain tumour progression‐related genes in colorectal cancer patients who have a postoperative intra‐abdominal infection, which in turn may promote the growth of residual cancer cells to become recurrent tumours.</jats:p></jats:sec>