title: Relationship between tumour PTEN/Akt/COX-2 expression, inflammatory response and survival in patients with colorectal cancer.
abstract: In patients with colorectal cancer (CRC), local and systemic inflammatory responses have been extensively reported to associate with cancer survival. However, the specific signalling pathways responsible for inflammatory responses are not clear. The PTEN/Akt pathway is a plausible candidate as it may play a role in mediating inflammation via COX-2, and has been associated with cancer progression. This study therefore examined the relationship between tumour PTEN/Akt/COX-2 expression, inflammatory responses and survival in CRC patients using a tissue microarray.In 201 CRC patients, activation of tumour-specific PTEN/Akt significantly associated with poorer CSS (12.0yrs v 7.3yrs, P=0.032), poorer differentiation (P=0.032), venous invasion (P=0.008) and peritoneal involvement (P=0.004). Patients were stratified for peri-nuclear expression of COX-2 to examine associations with inflammatory responses. In patients with absent peri-nuclear COX-2 expression, activation of tumour-specific PTEN/Akt significantly associated with poorer CSS (11.9yrs v 5.4yrs, P=0.001), poorer differentiation (P=0.018), venous invasion (P=0.003) and peritoneal involvement (P=0.001). However, no associations were seen with either the local or systemic inflammatory responses.In CRC patients, tumour-specific PTEN/Akt pathway activation was significantly associated with poorer CSS, particularly when peri-nuclear COX-2 expression was absent. However, activation of the PTEN/Akt pathway appears not to be responsible for the regulation of inflammatory responses.
authors.affiliation: Academic Unit of Surgery, School of Medicine, University of Glasgow, Royal Infirmary, Glasgow, United Kingdom.|Unit of Experimental Therapeutics, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Glasgow, United Kingdom.
authors.forename: Antonia K
authors.initials: AK
authors.lastname: Roseweir
authors.affiliation: Unit of Experimental Therapeutics, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Glasgow, United Kingdom.|Division of Cancer and Genetics, Cardiff University, Heath Park, Cardiff, United Kingdom.
authors.forename: Arfon G M T
authors.initials: AG
authors.lastname: Powell
authors.affiliation: Unit of Experimental Therapeutics, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Glasgow, United Kingdom.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Bennett
authors.affiliation: Academic Unit of Surgery, School of Medicine, University of Glasgow, Royal Infirmary, Glasgow, United Kingdom.
authors.forename: Hester C
authors.initials: HC
authors.lastname: Van Wyk
authors.affiliation: Academic Unit of Surgery, School of Medicine, University of Glasgow, Royal Infirmary, Glasgow, United Kingdom.
authors.forename: James
authors.initials: J
authors.lastname: Park
authors.affiliation: Academic Unit of Surgery, School of Medicine, University of Glasgow, Royal Infirmary, Glasgow, United Kingdom.
authors.forename: Donald C
authors.initials: DC
authors.lastname: McMillan
authors.affiliation: Academic Unit of Surgery, School of Medicine, University of Glasgow, Royal Infirmary, Glasgow, United Kingdom.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Horgan
authors.affiliation: Unit of Experimental Therapeutics, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Glasgow, United Kingdom.
authors.forename: Joanne
authors.initials: J
authors.lastname: Edwards
mesh_terms: D000368:Aged; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D051059:PTEN Phosphohydrolase / Q000096:biosynthesis*; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis*; D015398:Signal Transduction; D018746:Systemic Inflammatory Response Syndrome / Q000378:metabolism
chemical_list: D051546:Cyclooxygenase 2; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: Akt; COX-2; PTEN; colorectal cancer; inflammation