Circulating levels of soluble urokinase plasminogen activator receptor predict outcome after resection of biliary tract cancer

Loosen, Sven H.; Breuer, Annemarie; Tacke, Frank; Kather, Jakob Nikolas; Gorgulho, Joao; Alizai, Patrick H.; Bednarsch, Jan; Roeth, Anjali A.; Lurje, Georg; Schmitz, Sophia; Brozat, Jonathan F.; Paffenholz, Pia; Vucur, Mihael; Ritz, Thomas; Koch, Alexander; Ulmer, Tom Florian; Roderburg, Christoph; Longerich, Thomas; Neumann, Ulf; Luedde, Tom

doi:10.1016/j.jhepr.2020.100080

Cited by 19 publications

(20 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our data are in line with previous publications showing elevated suPAR serum levels in manifold cancers. Just recently, we demonstrated that concentrations of suPAR are elevated in patients with cholangiocellular carcinoma (CCA) [18] as well as in patients with pancreatic ductal adenocarcinoma (PDAC) [34] or colorectal cancer (CRC) [20]. Notably, serum concentrations of suPAR in our cohort of patients with NET are numerically very similar to those found in CCA, PDAC and CRC.…”

Section: Discussionsupporting

confidence: 70%

“…suPAR was identified as a biomarker in patients with inflammatory and infectious diseases [ 13 , 14 , 15 , 16 ]. Moreover, a prognostic role for suPAR serum levels has been demonstrated in different cancers including pancreatic, cholangiocellular and colorectal malignancies [ 17 , 18 , 19 , 20 ]. However, in NET no data on a potential role of circulating suPAR as a biomarker for prediction of patients’ prognosis or response to therapies have been reported so far.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Soluble Urokinase Plasminogen Activator Receptor (suPAR) Concentrations Are Elevated in Patients with Neuroendocrine Malignancies

Özdirik

Stueven

Knorr

et al. 2020

JCM

Self Cite

View full text Add to dashboard Cite

Neuroendocrine neoplasia (NEN) comprises heterogeneous tumors that are challenging to diagnose and, especially in cases of poorly differentiated (G3) NEN, are associated with very limited survival. Novel biomarkers allowing an early diagnosis as well as an optimal selection of suitable treatment options are urgently needed to improve the outcome of these patients. Recently, alterations of soluble urokinase-type plasminogen activator receptor (suPAR) serum levels were described in various types of cancers. However, the role of circulating suPAR as a biomarker in patients with NEN is unknown. In this study, we measured suPAR serum levels in a large and well-characterized cohort of 187 patients with NEN (neuroendocrine carcinomas (NEC) n = 30; neuroendocrine tumors (NET), n = 157) as well as 44 healthy controls. suPAR concentrations were significantly elevated in patients compared to controls. However, suPAR concentrations were independent of tumor-related factors such as the proliferation activity according to Ki-67, tumor grading, TNM (TNM classification of malignant tumors) stage, somatostatin receptor expression or clinical features such as functional or nonfunctional disease and the presence of tumor relapse. Interestingly, suPAR concentrations in NET patients were similar when compared to those measured in NEC patients. In contrast to previous results from other malignancies, in our analysis suPAR levels were not a significant predictor of overall survival. In conclusion, our data suggests that suPAR serum concentrations are elevated in NEN patients but do not allow prediction of outcome.

show abstract

Section: Discussionsupporting

confidence: 70%

Section: Introductionmentioning

confidence: 99%

Soluble Urokinase Plasminogen Activator Receptor (suPAR) Concentrations Are Elevated in Patients with Neuroendocrine Malignancies

Özdirik

Stueven

Knorr

et al. 2020

JCM

Self Cite

View full text Add to dashboard Cite

show abstract

“…expressed on epithelial and immune cells ( 9 ). Circulating suPAR has recently been associated with inflammatory diseases and several cancer entities ( 10 – 15 ). During systemic inflammation, an increased shedding of uPAR on circulating neutrophils has been reported as a source of elevated suPAR levels ( 16 ).…”

Section: Introductionmentioning

confidence: 99%

Serum Levels of Soluble Urokinase Plasminogen Activator Receptor Predict Tumor Response and Outcome to Immune Checkpoint Inhibitor Therapy

et al. 2021

Self Cite

View full text Add to dashboard Cite

BackgroundImmune checkpoint inhibitors (ICIs) have led to a paradigm shift in cancer therapy, improving outcomes in the treatment of various malignancies. However, not all patients benefit to the same extend from ICI. Reliable tools to predict treatment response and outcome are missing. Soluble urokinase plasminogen activator receptor (suPAR) is a marker of immune activation, whose levels are prognostic in various cancers. We evaluated circulating suPAR levels as a novel predictive and prognostic biomarker in patients receiving ICI therapy for solid tumors.MethodsA total of n = 87 patients receiving ICI therapy for different solid malignancies as well as 32 healthy controls were included into this study. Serum levels of suPAR were measured by ELISA prior to and sequentially at two time points during ICI therapy.ResultsBaseline suPAR serum levels were significantly higher in solid tumor patients compared to healthy controls. Importantly, patients with low suPAR levels both before or during ICI treatment were more likely to have a favorable response to treatment at three and six months, respectively. This finding was confirmed by multivariate binary logistic regression analysis including several clinicopathological parameters. Moreover, circulating suPAR levels before and during therapy were an independent prognostic factor for overall survival (OS). As such, patients with initial suPAR levels above our ideal prognostic cut-off value (4.86 ng/ml) had a median OS of only 160 days compared to 705 days for patients with suPAR levels below this cut-off value. Finally, low baseline suPAR levels identified a subgroup of patients who experienced ICI-related side effects which in turn were associated with favorable treatment response and outcome.ConclusionOur data suggest that measurements of suPAR serum levels are a previously unknown, easily accessible tool to predict individual treatment response and outcome to ICI therapy. Circulating suPAR might therefore be implemented into stratification algorithms to identify the ideal candidates for ICI treatment.

show abstract

“…Despite many different preinterventional stratification algorithms, such as the ART or SNACOR, optimal patient selection has remained challenging 6,8 . Soluble urokinase plasminogen activator receptor (suPAR) has been established as a promising novel biomarker reflecting the tumor biology in terms of grading or prognosis and allows us to guide preoperative treatment decisions regarding patients' outcomes in manifold cancers 9,10 . In the present study, we aimed at evaluating serum concentrations of suPAR as predictive and/or prognostic markers for patients undergoing TACE for primary and secondary liver cancer, independent of the disease etiology.…”

Section: Introductionmentioning

confidence: 99%

Elevated soluble urokinase plasminogen activator receptor serum levels indicate poor survival following transarterial chemoembolization therapy for hepatic malignancies: An exploratory analysis

et al. 2021

Self Cite

View full text Add to dashboard Cite

Background and Aim Transarterial chemoembolization (TACE) represents a standard of care for patients with intermediate‐stage hepatocellular carcinoma (HCC) or liver metastases. However, identification of the ideal candidates for TACE therapy remains challenging. The soluble urokinase plasminogen activator receptor (suPAR) has recently evolved as a prognostic marker in patients with cancer; however no data on suPAR in the context of TACE exists. Methods Serum levels of suPAR were measured by an enzyme‐linked immunosorbent assay in n = 48 TACE patients (HCC: n = 38, liver metastases: n = 10) before intervention and 1 day after TACE, as well as in 20 healthy controls. Results Serum levels of suPAR were significantly elevated in patients with liver cancer compared to healthy controls. Patients with or without an objective tumor response to TACE therapy had comparable levels of circulating suPAR. Importantly, baseline suPARs above the ideal prognostic cut‐off value (5.39 ng/mL) were a significant prognostic marker for reduced overall survival (OS) following TACE. As such, patients with initial suPAR levels >5.39 ng/mL showed a significantly reduced median OS of only 256 days compared to patients with suPAR serum levels below the cut‐off value (median OS: 611 days). In line with previous data, suPAR serum concentrations correlated with those of creatinine but were independent of tumor entity, leukocyte count, and C‐reactive protein in multivariate analysis. Conclusion Baseline suPAR serum levels provide important information on the postinterventional outcome of liver cancer patients receiving TACE.

show abstract

Circulating levels of soluble urokinase plasminogen activator receptor predict outcome after resection of biliary tract cancer

Cited by 19 publications

References 46 publications

Soluble Urokinase Plasminogen Activator Receptor (suPAR) Concentrations Are Elevated in Patients with Neuroendocrine Malignancies

Soluble Urokinase Plasminogen Activator Receptor (suPAR) Concentrations Are Elevated in Patients with Neuroendocrine Malignancies

Serum Levels of Soluble Urokinase Plasminogen Activator Receptor Predict Tumor Response and Outcome to Immune Checkpoint Inhibitor Therapy

Elevated soluble urokinase plasminogen activator receptor serum levels indicate poor survival following transarterial chemoembolization therapy for hepatic malignancies: An exploratory analysis

Contact Info

Product

Resources

About