Characteristics of patients with pancreatic cancer expressing a novel cancer cachectic factor

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Abstract
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 identified 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 patients 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 and was then identified by Western blotting of nitrocellulose membranes using a previously developed monoclonal antibody. Full nutritional assessment of 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 weight loss than patients whose urine did not contain PIF (median 12·5 (range 4–43) kg versus 4·5 (0–14) kg; P < 0·0002). No association was evident between the presence of PIF in patients' urine and serum C-reactive protein (CRP) concentration. Furthermore, the accelerated weight loss associated with PIF expression also appeared to be independent of the acute-phase response. Overall the presence of PIF was not associated with reduced survival, although 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 patients with a tumour of the pancreatic head. This observation appears to be independent of the effect of an increased hepatic acute-phase protein response.