title: 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.
abstract: OBJECTIVE
  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 (PBL) after surgery for colorectal cancer.
  
  
  METHODS
  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 (n = 23) and matched with patients without complications for the control group (n = 23). PBL were isolated from postoperative blood samples. Total RNA was extracted and hybridized to the Affymetrix Human Gene 1.0 ST microarray.
  
  
  RESULTS
  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 (S100P, HGF, MMP8, MMP9, PDGFC, IL1R2). Infection also upregulated some proangiogenic genes (CEP55, TRPS1) and downregulated some inhibitors of angiogenesis (MME, ALOX15, CXCL10). Finally, some inhibitors (HP, ORM1, OLFM4, IRAK3) and activators (GNLY, PRF1, FGFBP2) 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.
  
  
  CONCLUSIONS
  Analysis of PBL 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.
authors.affiliation: Section of Colon and Rectal Surgery, Department of Surgery, Hospital del Mar, Barcelona, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Alonso
authors.affiliation: Section of Colon and Rectal Surgery, Department of Surgery, Hospital del Mar, Barcelona, Spain.
authors.forename: X
authors.initials: X
authors.lastname: Mayol
authors.affiliation: Microarray Analysis Service, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Nonell
authors.affiliation: Section of Colon and Rectal Surgery, Department of Surgery, Hospital del Mar, Barcelona, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Salvans
authors.affiliation: Section of Colon and Rectal Surgery, Department of Surgery, Hospital del Mar, Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Pascual
authors.affiliation: Section of Colon and Rectal Surgery, Department of Surgery, Hospital del Mar, Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Pera
mesh_terms: D000368:Aged; D057868:Anastomotic Leak / Q000097:blood / Q000209:etiology; D016022:Case-Control Studies; D003082:Colectomy / Q000009:adverse effects; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000601:surgery; D005260:Female; D006801:Humans; D059413:Intraabdominal Infections / Q000097:blood* / Q000209:etiology; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000097:blood*; D011183:Postoperative Complications; D011446:Prospective Studies
chemical_list: D009363:Neoplasm Proteins
keywords: Colorectal cancer; intra-abdominal infection; microarrays; peripheral blood leucocytes; surgery; tumour recurrence