title: Plasma levels of miRNA-155 as a powerful diagnostic marker for dedifferentiated liposarcoma.
abstract: Atypic lipomatous tumors (ALT) and dedifferentiated liposarcomas (DDLS) are closely related liposarcoma subtypes, often difficult to distinguish but they exhibit an entirely different clinical outcome. Recently discovered regulatory functions of miRNAs in liposarcoma progression prompted us to investigate miRNAs as potential diagnostic biomarkers in liposarcoma with a main focus on circulating miRNAs for fast and reliable differential diagnosis. Tumor and blood samples of 35 patients with lipomatous lesions collected between June 2011 and September 2014 were analyzed by qRT-PCR. They included 10 lipomas, 7 ALT, 5 DDLS and 13 myxoid liposarcomas (MLS). Ten samples of normal fat tissue and blood from 20 healthy volunteers were used as controls. A meta-analysis of public data on miRNA expression in liposarcoma revealed 9 miRNAs with potential diagnostic power. Out of these, miRNA-155 was found significantly elevated in the circulation of DDLS patients as compared to the plasma levels detected in all other liposarcoma subtypes and in healthy subjects. miRNA-155 levels in the plasma samples correlated significantly (r=0.41, p=0.02) with those in corresponding tumor extracts. This correlation was even more pronounced in an analysis of plasma and tumor extracts of malignant liposarcoma subtypes alone (r=0.51, p=0.02). Receiver operating characteristic analysis indicated that plasma miRNA-155 levels have a high diagnostic accuracy for distinguishing DDLS from healthy subjects (AUC=0.91, p=0.005) and from lipomas (AUC=0.86, p=0.02), MLS (AUC=0.92, p=0.006) and most importantly ALT (AUC=0.91, p=0.01) patients. In conclusion, this study identified miRNA-155 as a first blood biomarker for the differential diagnosis of DDLS.
authors.affiliation: Laboratory for Orthopedic Research, Department of Orthopedics, Balgrist University Hospital, University of Zurich Forchstrasse 340, 8008 Zurich, Switzerland.
authors.forename: Aleksandar
authors.initials: A
authors.lastname: Boro
authors.affiliation: Laboratory for Orthopedic Research, Department of Orthopedics, Balgrist University Hospital, University of Zurich Forchstrasse 340, 8008 Zurich, Switzerland.
authors.forename: David
authors.initials: D
authors.lastname: Bauer
authors.affiliation: Laboratory for Orthopedic Research, Department of Orthopedics, Balgrist University Hospital, University of Zurich Forchstrasse 340, 8008 Zurich, Switzerland.
authors.forename: Walter
authors.initials: W
authors.lastname: Born
authors.affiliation: Laboratory for Orthopedic Research, Department of Orthopedics, Balgrist University Hospital, University of Zurich Forchstrasse 340, 8008 Zurich, Switzerland.
authors.forename: Bruno
authors.initials: B
authors.lastname: Fuchs
keywords: Liposarcoma; diagnostic biomarker; miRNA; plasma biomarker