Protein Expression Profiles Corresponding to Histological Changes with Denosumab Treatment in Giant Cell Tumors of Bone.

Purpose: Giant cell tumors of bone (GCTBs) are locally aggressive osteolytic bone tumors. Denosumab is a novel and effective therapeutic option for aggressive and recurrent GCTBs. Histologically, the post-denosumab-treated samples are characterized by two lesions: a residual stromal cell lesion with a few multinucleated giant cells (SL-lesion), and a fibro-osseous lesion (FO-lesion).

Experimental Design: To clarify the differences in the protein expression between the SL-lesion and FO-lesion in GCTB treated with denosumab, comparative proteomic studies are conducted using both lesions (12 pairs of pre- and post-denosumab treatment samples) by isobaric tags for relative and absolute quantification (i-TRAQ).

Results: Thirty-two consistently regulated proteins in the SL-lesions and 59 consistently regulated proteins in the FO-lesions are found. Twenty-one proteins in the SL-lesion and 48 proteins in the FO-lesion are independently expressed. These proteins may be involved in the process of the fibro-osseous reactions by denosumab treatment. In the software program used to establish these profiles, several canonical pathways are identified, including the unfolded protein response as an FO-lesion specific pathway.

Conclusions And Clinical Relevance: It is believed that the identified proteins and the results of the network analysis will provide a better understanding of the effects of denosumab in GCTB.