Intact and cleaved forms of the urokinase receptor enhance discrimination of cancer from non-malignant conditions in patients presenting with symptoms related to colorectal cancer

BACKGROUND: Colorectal cancer (CRC) is a leading cause of cancer-related morbidity and mortality in developed countries. It is known that early detection results in improved survival, and consequently there is a need for improved diagnostic tools in CRC. The plasma level of soluble urokinase plasminogen activator receptor (suPAR) was proposed as a marker in CRC patients. This study was undertaken to evaluate the individual molecular forms of suPAR as discriminators in a group of patients undergoing endoscopical examination following symptoms related to colorectal cancer. METHODS: In a case-control study comprising 308 patients undergoing endoscopical examination following CRC-related symptoms, 77 CRC patients with adenocarcinoma were age and gender matched to: 77 patients with adenomas; 77 with other non-malignant findings, and 77 with no findings. The different uPAR forms were measured in citrate plasma collected before endoscopical examination, using three different Time Resolved-Fluorescence Immuno Assays (TR-FIA's). RESULTS: All soluble uPAR forms were found to be significantly higher in cancer patients than in patients presenting with other nonmalignant findings; uPAR(I) P = 0.0006, suPAR(I-III) P<0.0001 and suPAR(I-III) + (II-III) P<0.0001, whereas no significant difference was found when performing similar comparisons for patients presenting with adenomas. The odds ratio (OR) for the comparison of uPAR(I) in patients with CRC to subjects with other non-malignant findings was 3.44 (95% CI: 1.86-6.37). CRC patients had a mean elevated level of 20.9% (95% CI: 10.2-32.6) for suPAR(I-III) and 18.5% (95% CI:9.0-28.8) for suPAR (I-III) + (II-III) compared with subjects with non-malignant findings. CONCLUSIONS: The findings confirm reports on increased uPAR expression in cancer patients and in particular elevated levels of suPAR in blood from CRC patients and indicate that suPAR levels in blood are increasing during carcinogenesis. Although none of the measured uPAR forms were cancer specific, our findings suggest that uPAR expression could be useful in the early detection of CRC when combined with other markers and clinical variables. British Journal of Cancer (2009) 101, 992-997. doi:10.1038/sj.bjc.6605228 www.bjcancer.com Published online 11 August 2009 (C) 2009 Cancer Research UK