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

Abstract

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.

Soluble Urokinase Plasminogen Activator Receptor (suPAR) Independently Predicts Severity and Length of Hospitalisation in Patients With COVID-19

“…Apart from urokinase plasminogen activator (uPA, also known as urokinase), uPAR interacts and cooperates with many ligands and receptors, primarily integrins, to facilitate intracellular signalling, cell migration, cell adhesion and tissue remodelling (20). Soluble uPAR (suPAR) results from proteolytic cleavage of uPAR (21), and has gained increased interest as circulating levels are found to reflect severity and prognosticate outcome of several malignant (22)(23)(24)(25)(26), autoimmune (27)(28)(29)(30) and infectious diseases (31)(32)(33)(34)(35)(36)(37). Additionally, suPAR is used in triaging of patients in acute care settings to early predict clinical deterioration due to suspected bacterial infections (38)(39)(40)(41)(42).…”

Prospective Phase II Trial of Prognostication by 68Ga-NOTA-AE105 uPAR PET in Patients with Neuroendocrine Neoplasms: Implications for uPAR-Targeted Therapy

“…Previously, our group has investigated uPAR expression by immunohistochemical staining of primary tumor or metastasis from patients with NEN G3 (Ki67 >20%) showing uPAR expression in stromal and or tumor cells in 16/21 (76%) patients (25). However, to the best of our knowledge, expression of uPAR in patients with low grade NEN has never been studied in situ but only indirectly by measurement of soluble uPAR (suPAR) in serum (26). suPAR is the cleaved version of the membrane-bound uPAR and may thus be measured as a circulating uPAR biomarker.…”

The Role of Soluble Urokinase Plasminogen Activator Receptor (suPAR) in the Context of Aneurysmal Subarachnoid Hemorrhage (aSAH)—A Prospective Observational Study

“…Since inflammation is a universal response of the body to various conditions such as tumors, trauma, and ischemia, recent scientific studies investigated the use of inflammatory biomarkers to predict poor outcome. SuPAR has already been shown to be a useful predictor of outcome in patients with neoplasia of the hepatobiliary system and pancreas, as well as neuroendocrine malignancies (24)(25)(26). The prognostic significance of suPAR for poor outcome in traumatic brain injury (TBI) and stroke has also been demonstrated (27,28).…”