Secretomics identifies follistatin as a predictive biomarker for response to treatment with tyrosine kinase inhibitors in synovial sarcoma

DOI Web Site 参考文献41件
  • Qiao Zhiwei
    Division of Rare Cancer Research, National Cancer Center Research Institute
  • Kito Fusako
    Department of Innovative Seeds Evaluation, National Cancer Center Research Institute
  • Takai Yoko
    Department of Innovative Seeds Evaluation, National Cancer Center Research Institute
  • Oyama Rieko
    Department of Innovative Seeds Evaluation, National Cancer Center Research Institute
  • Kondo Tadashi
    Division of Rare Cancer Research, National Cancer Center Research Institute Department of Innovative Seeds Evaluation, National Cancer Center Research Institute

抄録

<p>Sarcoma is a rare malignancy with an aggressive clinical course. Tyrosine kinase inhibitors (TKIs) have emerged as effective drugs in targeted therapy for malignancies; in particular, pazopanib was recently approved for the treatment of sarcoma. However, as only a limited proportion of patients exhibit favorable response to treatment with TKIs, predictive biomarkers of response to these drugs are urgently needed. In this study, we attempted to identify predictive biomarkers for response to TKIs in synovial sarcoma. We performed a magnetic bead–based assay (Bio-Plex) using synovial sarcoma cell culture supernatant and validated the results by ELISA and western blotting. Cellular protein and mRNA expression levels of candidate biomarkers were evaluated by western blotting and RT-PCR. Gene expression profiling of candidate biomarkers was conducted by meta-analysis of publicly available gene expression data from 149 patients with synovial sarcoma. We found that follistatin (FST) was significantly highly expressed in TKI-resistant cells. Moreover, cell proliferation was decreased following gene silencing of FST. Meta-analysis revealed that the mRNA expression of FST varied among the 149 patients with synovial sarcoma, and that 23 genes were co-expressed with FST; these included genes encoding receptor tyrosine kinase-like orphan receptor 1, Sal-like protein 4, and signal transducer CD24. This study suggested that FST represents a candidate predictive biomarker for response to treatment with TKIs in synovial sarcoma. Secretomics is a promising approach for predictive biomarker exploration. The utility of FST as a predictive biomarker for response to treatment with TKIs in synovial sarcoma should be further validated using clinical samples.</p>

収録刊行物

参考文献 (41)*注記

もっと見る

キーワード

詳細情報 詳細情報について

問題の指摘

ページトップへ