Background: Recently a novel tumour-derived cachectic factor was identified
in the murine MAC16 colonic adenocarcinoma model of cachexia. This factor,
provisionally named proteolysis-inducing factor (PIF), was subsequently id
entified in the urine of weight-losing patients with cancer but not in the
urine of weight-stable patients with cancer or weight-losing controls with
benign disease. This study determined the nutritional characteristics of pa
tients with pancreatic cancer who excrete PIF in the urine and investigated
the relationship between PIF and the acute-phase protein response.
Methods: PIF was isolated from urine by precipitation and ultrafiltration a
nd was then identified by Western blotting of nitrocellulose membranes usin
g a previously developed monoclonal antibody. Full nutritional assessment o
f patients was undertaken at the same time as urine collection.
Results: PIF was detected in the urine of 80 per cent of patients (n = 55).
These patients had a significantly greater total weight loss and rate of w
eight loss than patients whose urine did not contain PIF (median 12.5 (rang
e 4-43) kg versus 4.5 (0-14) kg; P < 0.0002). No association was evident be
tween the presence of PIF in patients' urine and serum C-reactive protein (
CRP) concentration. Furthermore, the accelerated weight loss associated wit
h PIF expression also appeared to be independent of the acute-phase respons
e. Overall the presence of PIF was not associated with reduced survival, al
though the previously reported association between raised CRP concentration
and poor prognosis was confirmed.
Conclusion: PIF is associated with an accelerated rate of weight loss in pa
tients with a tumour of the pancreatic head. This observation appears to be
independent of the effect of an increased hepatic acute-phase protein resp
onse.