Secretomics鉴定卵泡listatin作为滑膜肉瘤中酪氨酸激酶抑制剂治疗反应的预测性生物标志物

Zhiwei Qiao, F. Kito, Y. Takai, R. Oyama, T. Kondo
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引用次数: 2

摘要

肉瘤是一种罕见的恶性肿瘤,具有侵袭性的临床病程。酪氨酸激酶抑制剂(TKIs)已成为恶性肿瘤靶向治疗的有效药物;特别是,帕唑帕尼最近被批准用于治疗肉瘤。然而,由于只有有限比例的患者对TKIs治疗表现出良好的反应,因此迫切需要对这些药物反应的预测性生物标志物。在这项研究中,我们试图确定滑膜肉瘤对TKIs反应的预测性生物标志物。我们使用滑膜肉瘤细胞培养上清进行磁珠检测(Bio-Plex),并通过ELISA和western blotting验证结果。采用western blotting和RT-PCR检测候选生物标志物的细胞蛋白和mRNA表达水平。通过荟萃分析149例滑膜肉瘤患者的公开基因表达数据,对候选生物标志物进行基因表达谱分析。我们发现卵泡listatin (FST)在tki耐药细胞中显著高表达。此外,FST基因沉默后,细胞增殖能力下降。meta分析显示,149例滑膜肉瘤患者中FST mRNA表达存在差异,其中23个基因与FST共表达;这些基因包括编码酪氨酸激酶样孤儿受体1、sal样蛋白4和信号传感器CD24的基因。这项研究表明,FST是滑膜肉瘤TKIs治疗反应的候选预测性生物标志物。分泌组学是一种很有前途的预测性生物标志物探索方法。FST作为滑膜肉瘤TKIs治疗反应的预测性生物标志物的效用应通过临床样本进一步验证。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Secretomics identifies follistatin as a predictive biomarker for response to treatment with tyrosine kinase inhibitors in synovial sarcoma
SUMMARY 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.
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