Increased cathepsin D protein expression is a biomarker for osteosarcomas, pulmonary metastases and other bone malignancies
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Timo Gemoll1, Franziska Epping1, Lisa Heinrich1, Britta Fritzsche1, Uwe J. Roblick1, Silke Szymczak2, Sonja Hartwig3, Reinhard Depping4, Hans-Peter Bruch1, Christoph Thorns5, Stefan Lehr3, Andreas Paech6,* and Jens K. Habermann1,*
1 Section for Translational Surgical Oncology and Biobanking, Department of Surgery, University of Lübeck and University Medical Center Schleswig-Holstein, Lübeck, Germany
2 Institute of Medical Informatics and Statistics, University Medical Center Schleswig-Holstein, Kiel, Germany
3 Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Center (DZD), Düsseldorf, Germany
4 Institute for Physiology, University of Lübeck, Lübeck, Germany
5 Institute of Pathology, University Medical Center Schleswig-Holstein, Lübeck, Germany
6 Department of Orthopaedics and Traumatology, University Medical Center Schleswig Holstein, Lübeck, Germany
* These authors have contributed equally to this work
Jens K. Habermann, email:
Keywords: osteosarcoma; bone malignancies; two-dimensional gel electrophoresis; CTSD; mass spectrometry
Received: February 18, 2015 Accepted: April 22, 2015Published: May 14, 2015
Cancer proteomics provide a powerful approach to identify biomarkers for personalized medicine. Particularly, biomarkers for early detection, prognosis and therapeutic intervention of bone cancers, especially osteosarcomas, are missing. Initially, we compared two-dimensional gel electrophoresis (2-DE)-based protein expression pattern between cell lines of fetal osteoblasts, osteosarcoma and pulmonary metastasis derived from osteosarcoma. Two independent statistical analyses by means of PDQuest® and SameSpot® software revealed a common set of 34 differentially expressed protein spots (p < 0.05). 17 Proteins were identified by mass spectrometry and subjected to Ingenuity Pathway Analysis resulting in one high-ranked network associated with Gene Expression, Cell Death and Cell-To-Cell Signaling and Interaction. Ran/TC4-binding protein (RANBP1) and Cathepsin D (CTSD) were further validated by Western Blot in cell lines while the latter one showed higher expression differences also in cytospins and in clinical samples using tissue microarrays comprising osteosarcomas, metastases, other bone malignancies, and control tissues. The results show that protein expression patterns distinguish fetal osteoblasts from osteosarcomas, pulmonary metastases, and other bone diseases with relevant sensitivities between 55.56% and 100% at ≥87.50% specificity. Particularly, CTSD was validated in clinical material and could thus serve as a new biomarker for bone malignancies and potentially guide individualized treatment regimes.
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