High baseline soluble urokinase plasminogen activator receptor (suPAR) serum levels indicate adverse outcome after resection of pancreatic adenocarcinoma

Abstract

Surgical resection represents the only potentially curative therapy for patients with pancreatic adenocarcinoma (PDAC), an aggressive malignancy with a very limited 5-year survival rate. However, even after complete tumor resection, many patients are still facing an unfavorable prognosis underlining the need for better preoperative stratification algorithms. Here, we explored the role of the secreted glycoprotein soluble urokinase plasminogen activator receptor (suPAR) as a novel circulating biomarker for patients undergoing resection of PDAC. Serum levels of suPAR were measured by enzyme-linked immunosorbent assay (ELISA) in an exploratory as well as a validation cohort comprising a total of 127 PDAC patients and 75 healthy controls. Correlating with a cytoplasmic immunohistochemical expression of uPAR in PDAC tumor cells, serum levels of suPAR were significantly elevated in PDAC patients compared to healthy controls and patient with PDAC precursor lesions. Importantly, patients with high preoperative suPAR levels above a calculated cutoff value of 5.956 ng/ml showed a significantly reduced overall survival after tumor resection. The prognostic role of suPAR was further corroborated by uni- and multivariate Cox-regression analyses including parameters of systemic inflammation, liver and kidney function as well as clinico-pathological patients’ characteristics. Moreover, high baseline suPAR levels identified those patients particularly susceptible to acute kidney injury and surgical complications after surgery. In conclusion, our data suggest that circulating suPAR represents a novel prognostic marker in PDAC patients undergoing tumor resection that might be a useful addition to existing preoperative stratification algorithms for identifying patients that particularly benefit from extended tumor resection.

Circulating levels of microRNA193a-5p predict outcome in early stage hepatocellular carcinoma

“…Statistical analyses were performed as recently described [12]. qPCR data is displayed as relative serum levels.…”

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

“…Our study provided evidence that elevated suPAR levels both before treatment initiation and during the course of treatment predict poor response and outcome to ICI. Although suPAR has been described as a prognostic marker for different treatment modalities (e.g., tumor resection, chemotherapy) of various cancer entities ( 10 , 14 , 28 ), this is the first study to evaluate its relevance in the context of ICI therapy. Nevertheless, the underlying molecular mechanism linking elevated suPAR levels with a poor response and outcome to ICI remains unknown.…”

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

“…Neuroendocrine neoplasia represents a rare but sometimes highly aggressive type of cancer [29,30]. Surgical tumor resection is the only available curative treatment option but the patients' long-term outcome, even after successful tumor resection, is often limited due to high risk of recurrence [31,32]. At present, the only clinically available tumor marker, Chromogranin A (CgA), has been demonstrated to be of limited sensitivity and specificity and is in most cases only used to monitor tumor response to chemotherapy [10].…”