Elevated serum levels of bone sialoprotein (BSP) predict long-term mortality in patients with pancreatic adenocarcinoma

Sven H Loosen,Martina Spehlmann,Ulf P Neumann,Frank Tacke,Christian Trautwein,Christoph Roderburg,Tom Luedde,Mark Luedde,Sanchari Roy,Niklas Puethe,Tom F Ulmer,Pia Hoening,David V Cardenas

doi:10.1038/s41598-018-38352-2

Sven H Loosen, Martina Spehlmann + Show 11 more

Open Access

https://doi.org/10.1038/s41598-018-38352-2

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Abstract

Patients with pancreatic adenocarcinoma (PDAC) still face a very limited prognosis. At early stage, surgical tumor resection might offer long-term survival but disease recurrence is common and the existing stratification algorithms are often unsuitable to identify patients who particularly benefit from surgery. Here, we investigated the potential role of bone sialoprotein (BSP) as a circulating marker in patients undergoing resection of PDAC. We used ELISA to determine serum concentrations of BSP in a cohort of 132 PDAC patients as well as 39 healthy controls. Circulating BSP levels were significantly higher in PDAC patients compared to healthy controls. Notably, elevated preoperative BSP levels above the ideal cut-off value of 4743 pg/ml turned out as a significant predictor for an impaired postoperative survival. The potential of preoperative BSP levels as a prognostic marker was further underlined by uni- and multivariate Cox-regression analyses including various tumour- and patient-specific. Finally, high tumoral BSP expression was also associated with a significantly impaired long-term survival. In conclusion, we identified a novel role of circulating BSP as a biomarker in PDAC patients undergoing tumor resection. Such data might help to establish new preoperative stratification strategies to better identify patients who particularly benefit from tumor resection.

Highlights

Patients with pancreatic adenocarcinoma (PDAC) still face a very limited prognosis
We found that pancreatic cancer patients display a significant elevation of bone sialoprotein (BSP) serum levels compared to healthy controls (Fig. 1a and Supplementary Table 1)
The diagnostic power of serum BSP levels (AUCBSP: 0.665) for the differentiation of pancreatic cancer patients and healthy controls was inferior to tumor markers such as CA19-9 and CEA (AUCCA19-9: 0.908, AUCCEA: 0.786, Fig. 1b), the combinational use of BSP and CA19-9 was superior to each serum marker alone (AUCBSP/CA19-9: 0.931, Fig. 1c)

Summary

Introduction

Patients with pancreatic adenocarcinoma (PDAC) still face a very limited prognosis. At early stage, surgical tumor resection might offer long-term survival but disease recurrence is common and the existing stratification algorithms are often unsuitable to identify patients who benefit from surgery. The stroma and the tumor itself express various proteins, which have been proven to be prognostic biomarkers[9,10] In this context, “small integrin binding ligand N-linked glycoproteins” (SIBLINGs) have gained increasing interest due to their specific role in the regulation of tumor cell proliferation, angiogenesis and metastasis as well as their involvement in molecular processes in pancreatic cancer[11]. With respect to circulating levels of the SIBLINGs-family, elevated serum levels of osteopontin were found in PDAC patients and correlated with disease stages and an impaired patients’ prognosis[15,16]. It is presently unknown if circulating levels of BSP play a similar role as a diagnostic and/or prognostic biomarker in PDAC patients. We measured BSP serum levels in 132 PDAC patients at different stage of disease that underwent surgical tumor resection at our tertiary referral centre

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