Preoperative plasma soluble urokinase plasminogen activator receptor as a prognostic marker in rectal cancer patients. An EORTC-Receptor and Biomarker Group collaboration

Background and aims Since approximately 30% of patients with Dukes’ stage B colorectal cancer will experience disease recurrence within five years of primary treatment, current staging of patients with early colorectal cancer apparently fails to adequately predict patient outcome. It has previously been shown that the preoperative plasma concentration of soluble urokinase plasminogen activator receptor (suPAR) is associated with the survival of patients with early colorectal cancer. In this study we sought to confirm the independent prognostic value of suPAR in rectal cancer. Methods suPAR was retrospectively determined by two different versions of a suPAR ELISA in preoperatively collected plasma samples from a Swedish (n=354) and a Danish (n=255) cohort of rectal cancer patients. Results In both cohorts the suPAR concentration was significantly higher in Dukes’ stage D patients than in Dukes’ stage A-C patients (p<0.0001). Among Dukes’ stage A-C patients, no differences in median suPAR values were seen. In univariate analysis, continuous suPAR was found to be associated with survival (p<0.0001 in both cohorts). Of particular interest was that similar results were obtained for Dukes’ stage A and B patients when analyzed separately. In multivariate analysis, continuous suPAR was found in both cohorts to be independent of Dukes’ stage. Conclusions This study confirms that the preoperative concentration of plasma suPAR contains independent prognostic information on patients with rectal cancer. This result was independent of the two different versions of an in-house suPAR ELISA used to perform the analyses. The next step in the evaluation of suPAR as a prognostic parameter in rectal cancer will be to launch an appropriately dimensioned prospective study where the benefit of applying preoperative plasma suPAR measurement to clinical decision-making regarding adjuvant therapy is assessed.

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Soluble urokinase plasminogen activator receptor (suPAR) as a prognostic marker of mortality in healthy, general and patient populations: protocol for a systematic review and meta-analysis

BMJ Open ◽

10.1136/bmjopen-2019-036125 ◽

2020 ◽

Vol 10 (7) ◽

pp. e036125 ◽

Cited By ~ 1

Author(s):

Jens Emil Vang Petersen ◽

Thomas Kallemose ◽

Karen D Barton ◽

Avshalom Caspi ◽

Line Jee Hartmann Rasmussen

Keyword(s):

Systematic Review ◽

Plasminogen Activator ◽

Chronic Inflammation ◽

Prognostic Marker ◽

Meta Analysis ◽

Urokinase Plasminogen Activator ◽

Urokinase Plasminogen Activator Receptor ◽

Improve Risk Stratification ◽

Population Type ◽

Plasminogen Activator Receptor

IntroductionChronic inflammation is increasingly recognised as a major contributor to disease, disability and ultimately death, but measuring the levels of chronic inflammation remains non-canonised, making it difficult to relate chronic inflammation and mortality. Soluble urokinase plasminogen activator receptor (suPAR), an emerging biomarker of chronic inflammation, has been proposed as a prognostic biomarker associated with future incidence of chronic disease and mortality in general as well as patient populations. Proper prognostic biomarkers are important as they can help improve risk stratification in clinical settings and provide guidance in treatment or lifestyle decisions as well as in the design of randomised trials. Here, we wish to summarise the evidence about the overall association of the biomarker suPAR with mortality in healthy, general and patient populations across diseases.Methods and analysisThe search will be conducted using Medline, Embase and Scopus databases from their inception to 03 June 2020 to identify studies investigating ‘suPAR’ and ‘mortality’. Observational studies and control groups from intervention studies written in English or Danish will be included. The ‘Quality In Prognosis Studies’ tool will be used to assess the risk of bias for the studies included. Unadjusted and adjusted mortality outcome measures (eg, risk ratios, ORs, HRs) with 95% CIs will be extracted for healthy individuals, general and patient populations. The primary outcome is all-cause mortality within any given follow-up. Subgroup analyses will be performed based on time of outcome, cause of death, population type, adjustments for conventional risk factors and inflammation markers.Ethics and disseminationThis systematic review will synthesise evidence on the use of suPAR as a prognostic marker for mortality. The results will be disseminated by publication in a peer-reviewed journal. Data used will be obtained from published studies, and ethics approval is therefore not necessary for this systematic review.Trial registration number PROSPEROCRD42020167401.

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