title: Elevated tumour interleukin-1beta is associated with systemic inflammation: A marker of reduced survival in gastro-oesophageal cancer.
abstract: Systemic inflammation is associated with adverse prognosis cancer but its aetiology remains unclear. We investigated the expression of proinflammatory cytokines within normal mucosa from healthy controls and tumour tissue in cancer patients and related these levels with markers of systemic inflammation and with the presence of a tumour inflammatory infiltrate. Tissue was collected from 56 patients with gastro-oesophageal cancer and from 12 healthy controls. Tissue cytokine mRNA concentrations were measured by real-time PCR and tissue protein concentrations by cytometric bead array. The degree of chronic inflammatory cell infiltrate was recorded. Serum cytokine and acute phase protein concentrations (including C-reactive protein (CRP)) were measured by enzyme-linked immunosorbent assay. Proinflammatory cytokines were significantly overexpressed (interleukin (IL)-1beta, IL-6, IL-8 and tumour necrosis factor-alpha) both at mRNA and protein levels in the cancer specimens compared with mucosa from controls. Interleukin-1beta was expressed in greatest (10-100-fold) concentration and protein levels correlated significantly with systemic inflammation (CRP) (P = 0.05, r = 0.31). A chronic inflammatory infiltrate was observed in 75% of the cancer specimens and was associated with systemic inflammation (CRP: P = 0.01). However, the presence of chronic inflammation per se was not associated with altered cytokine expression within the tumour. Both a chronic inflammatory infiltrate and systemic inflammation (CRP) were associated with reduced survival (P = 0.05 and P = 0.03, respectively). Tumour chronic inflammatory infiltrate and tumour tissue IL-1beta overexpression are potential independent factors influencing systemic inflammation in oesophagogastric cancer patients.
authors.affiliation: Tissue Injury and Repair Group, Department of Clinical and Surgical Sciences, MRC Centre for Inflammation Research, The Chancellor's Building, Edinburgh University, 49 Little France Crescent, Edinburgh EH16 4SB, UK.
authors.forename: D A C
authors.initials: DA
authors.lastname: Deans
authors.forename: S J
authors.initials: SJ
authors.lastname: Wigmore
authors.forename: H
authors.initials: H
authors.lastname: Gilmour
authors.forename: S
authors.initials: S
authors.lastname: Paterson-Brown
authors.forename: J A
authors.initials: JA
authors.lastname: Ross
authors.forename: K C H
authors.initials: KC
authors.lastname: Fearon
mesh_terms: D000209:Acute-Phase Proteins / Q000032:analysis; D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D016207:Cytokines / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D004943:Esophagogastric Junction / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D053583:Interleukin-1beta / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D016019:Survival Analysis
chemical_list: D000209:Acute-Phase Proteins; D014408:Biomarkers, Tumor; D016207:Cytokines; D053583:Interleukin-1beta; D012333:RNA, Messenger