Increased cathepsin D protein expression is a biomarker for osteosarcomas, pulmonary metastases and other bone malignancies

TY - JOUR

T1 - Increased cathepsin D protein expression is a biomarker for osteosarcomas, pulmonary metastases and other bone malignancies

AU - Gemoll, Timo

AU - Epping, Franziska

AU - Heinrich, Lisa

AU - Fritzsche, Britta

AU - Roblick, Uwe J

AU - Szymczak, Silke

AU - Hartwig, Sonja

AU - Depping, Reinhard

AU - Bruch, Hans-Peter

AU - Thorns, Christoph

AU - Lehr, Stefan

AU - Paech, Andreas

AU - Habermann, Jens K

PY - 2015/6/30

Y1 - 2015/6/30

N2 - 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.

AB - 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.

KW - Biomarkers, Tumor

KW - Bone Neoplasms

KW - Cathepsin D

KW - Cell Line, Tumor

KW - Electrophoresis, Gel, Two-Dimensional

KW - Gene Expression Profiling

KW - Humans

KW - Lung Neoplasms

KW - Mass Spectrometry

KW - Neoplasm Proteins

KW - Nuclear Proteins

KW - Osteoblasts

KW - Osteosarcoma

KW - Proteomics

KW - Tissue Array Analysis

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.18632/oncotarget.4140

DO - 10.18632/oncotarget.4140

M3 - SCORING: Journal article

C2 - 26203049

VL - 6

SP - 16517

EP - 16526

JO - ONCOTARGET

JF - ONCOTARGET

SN - 1949-2553

IS - 18

ER -