title: Increased cathepsin D protein expression is a biomarker for osteosarcomas, pulmonary metastases and other bone malignancies.
abstract: 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.
authors.affiliation: Section for Translational Surgical Oncology and Biobanking, Department of Surgery, University of Lübeck and University Medical Center Schleswig-Holstein, Lübeck, Germany.
authors.forename: Timo
authors.initials: T
authors.lastname: Gemoll
authors.affiliation: Section for Translational Surgical Oncology and Biobanking, Department of Surgery, University of Lübeck and University Medical Center Schleswig-Holstein, Lübeck, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Epping
authors.affiliation: Section for Translational Surgical Oncology and Biobanking, Department of Surgery, University of Lübeck and University Medical Center Schleswig-Holstein, Lübeck, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Heinrich
authors.affiliation: Section for Translational Surgical Oncology and Biobanking, Department of Surgery, University of Lübeck and University Medical Center Schleswig-Holstein, Lübeck, Germany.
authors.forename: Britta
authors.initials: B
authors.lastname: Fritzsche
authors.affiliation: Section for Translational Surgical Oncology and Biobanking, Department of Surgery, University of Lübeck and University Medical Center Schleswig-Holstein, Lübeck, Germany.
authors.forename: Uwe J
authors.initials: UJ
authors.lastname: Roblick
authors.affiliation: Institute of Medical Informatics and Statistics, University Medical Center Schleswig-Holstein, Kiel, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Szymczak
authors.affiliation: Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Center (DZD), Düsseldorf, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Hartwig
authors.affiliation: Institute for Physiology, University of Lübeck, Lübeck, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Depping
authors.affiliation: Section for Translational Surgical Oncology and Biobanking, Department of Surgery, University of Lübeck and University Medical Center Schleswig-Holstein, Lübeck, Germany.
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Bruch
authors.affiliation: Institute of Pathology, University Medical Center Schleswig-Holstein, Lübeck, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Thorns
authors.affiliation: Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Center (DZD), Düsseldorf, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Lehr
authors.affiliation: Department of Orthopaedics and Traumatology, University Medical Center Schleswig Holstein, Lübeck, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Paech
authors.affiliation: Section for Translational Surgical Oncology and Biobanking, Department of Surgery, University of Lübeck and University Medical Center Schleswig-Holstein, Lübeck, Germany.
authors.forename: Jens K
authors.initials: JK
authors.lastname: Habermann
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D001859:Bone Neoplasms / Q000473:pathology*; D002402:Cathepsin D / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D015180:Electrophoresis, Gel, Two-Dimensional; D020869:Gene Expression Profiling; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary*; D013058:Mass Spectrometry; D009363:Neoplasm Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics; D010006:Osteoblasts / Q000378:metabolism; D012516:Osteosarcoma / Q000473:pathology*; D040901:Proteomics; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C091775:ran-binding protein 1; C533922:CTSD protein, human; D002402:Cathepsin D
keywords: CTSD; bone malignancies; mass spectrometry; osteosarcoma; two-dimensional gel electrophoresis