Expression of the proteolysis-inducing factor core peptide mRNA is upregulated in both tumour and adjacent normal tissue in gastro-oesophageal malignancy.
Gastro-oesophageal cancer is associated with a high incidence of cachexia. Proteolysis-inducing factor (PIF) has been identified as a possible cachectic factor and studies suggest that PIF is produced exclusively by tumour cells. We investigated PIF core peptide (PIF-CP) mRNA expression in tumour and benign tissue from patients with gastro-oesophageal cancer and in gastro-oesophageal biopsies for healthy volunteers. Tumour tissue and adjacent benign tissue were collected from patients with gastric and oesophageal cancer (n=46) and from benign tissue only in healthy controls (n=11). Expression of PIF-CP mRNA was quantified by real-time PCR. Clinical and pathological information along with nutritional status was collected prospectively. In the cancer patients, PIF-CP mRNA was detected in 27 (59%) tumour samples and 31 (67%) adjacent benign tissue samples. Four (36%) gastro-oesophageal biopsies from healthy controls also expressed PIF-CP mRNA. Expression was higher in tumour tissue (P=0.031) and benign tissue (P=0.022) from cancer patients compared with healthy controls. In the cancer patients, tumour and adjacent benign tissue PIF-CP mRNA concentrations were correlated with each other (P<0.0001, r=0.73) but did not correlate with weight loss or prognosis. Although PIF-CP mRNA expression is upregulated in both tumour and adjacent normal tissue in gastro-oesophageal malignancy, expression does not relate to prognosis or cachexia. Post-translational modification of PIF may be a key step in determining the biological role of PIF in the patient with advanced cancer and cachexia.
Deans
D A C
DA
Department of Clinical and Surgical Sciences, Cell Injury and Apoptosis Section, Tissue Injury and Repair Group, Edinburgh University, Chancellor's Building SU227, 49 Little France Crescent, Edinburgh EH16 4SB, UK.
Wigmore
S J
SJ
Gilmour
H
H
Tisdale
M J
MJ
Fearon
K C H
KC
Ross
J A
JA
D000368:Aged; D001706:Biopsy; D001798:Blood Proteins / Q000096:biosynthesis* / Q000502:physiology; D002100:Cachexia / Q000209:etiology / Q000235:genetics / Q000503:physiopathology*; D016022:Case-Control Studies; D004938:Esophageal Neoplasms / Q000150:complications* / Q000235:genetics* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011499:Protein Processing, Post-Translational; D011509:Proteoglycans; D012333:RNA, Messenger / Q000096:biosynthesis; D013274:Stomach Neoplasms / Q000150:complications* / Q000235:genetics* / Q000473:pathology; D015854:Up-Regulation
D001798:Blood Proteins; D011509:Proteoglycans; D012333:RNA, Messenger; C042057:proteolysis-inducing peptide