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.
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.
D A C
DA
Deans
S J
SJ
Wigmore
H
H
Gilmour
M J
MJ
Tisdale
K C H
KC
Fearon
J A
JA
Ross
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