Protein Expression Profiles Corresponding to Histological Changes with Denosumab Treatment in Giant Cell Tumors of Bone.
Protein Expression Profiles Corresponding to Histological Changes with Denosumab Treatment in Giant Cell Tumors of Bone.
复制标题
与狄诺塞麦治疗骨巨细胞瘤的组织学变化相对应的蛋白质表达谱。
DOI：
10.1002/prca.201800147
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发表时间：
2019
期刊：
影响因子：
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通讯作者：
Saito T.
中科院分区：
文献类型：
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作者：
Suehara Y;Okubo T;Kurihara T;Hayashi T;Kohsaka S;Kazuno S;Sano K;Hasegawa N;Miura Y;Akaike K;Kim Y;Takamochi K;Takahashi F;Ueno T;Kaneko K;Saito T.
骨巨细胞瘤是一种具有局部侵袭性的溶骨性骨肿瘤。地舒单抗是侵袭性和复发性GCTB的一种新型有效治疗选择。在组织学上，地舒单抗处理后的样本具有两处病变特征：残留的基质细胞病变伴少量多核巨细胞（SL病变）和骨间病变实验设计为了阐明地舒单抗治疗的GCTB中SL病变和FO病变之间蛋白表达的差异，使用两种病变进行比较蛋白质组学研究（12对地舒单抗给药前和给药后样本），通过同量异位素标签进行相对和绝对定量（i-TRAQ）结果在SL-病变和FO-病变中分别检测到32个和59个一致性调节蛋白，其中SL-病变中有21个和FO-病变中有48个蛋白独立表达。这些蛋白质可能参与地舒单抗处理的骨反应过程。在用于建立这些图谱的软件程序中，鉴定了几种典型途径，包括作为FO-病变特异性途径的未折叠蛋白反应。结论和临床意义据信，所鉴定的蛋白和网络分析的结果将更好地理解地舒单抗在GCTB中的作用。
PurposeGiant 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 designTo 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).ResultsThirty‐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 relevanceIt 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.