Analysis of global
protein expression, an approach known as expression proteomics, can offer important clues for understanding
tumor biology that cannot be obtained by other approaches (e.g., genome or transcriptome analysis). Using two-dimensional difference gel electrophoresis (2D-DIGE) and mass spectrometry, we performed global
protein expression studies of bone and
soft tissue sarcomas to develop novel diagnostic and therapeutic
biomarkers and allow molecular classification of the
tumors. Among 1500
protein variants identified in the two-dimensional gel, 67
proteins correctly distinguished the eight subtypes of 99 histologically classified
soft tissue sarcomas. Hierarchical clustering demonstrated
leiomyosarcoma and MFH shared a similar
protein expression profile, and
clear cell sarcoma,
synovial sarcoma, and
MPNST could be grouped according to their
protein expression patterns. Pleomorphic
leiomyosarcoma and MFH showed similar
tropomyosin isoform expression patterns. Patients with
gastrointestinal stromal tumors expressing pfetin
protein had better survival than those whose
tumors lacked it. We identified 10
protein spots associated with the chemosensitivity of
osteosarcoma to preoperative
chemotherapy. These 10 spots could be new diagnostic and prognostic markers for
osteosarcoma and new therapeutic targets for the disease. Proteomic analysis using 2D-DIGE provides novel information on the biology of bone and
soft tissue sarcomas that could be used to diagnosis and treat these
tumors.
LEVEL OF EVIDENCE: Level II, diagnostic study. See the Guidelines for Authors for a complete description of levels of evidence.