Identification of novel candidate circulating biomarkers for malignant soft tissue sarcomas: Correlation with metastatic progression
Identification of novel candidate circulating biomarkers for malignant soft tissue sarcomas: Correlation with metastatic progression
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DOI：
10.1002/pmic.201500164
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发表时间：
2016-02-01
期刊：
影响因子：
3.4
通讯作者：
Benassi, Maria Serena
中科院分区：
文献类型：
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作者：
Conti, Amalia;Fredolini, Claudia;Benassi, Maria Serena
软组织肉瘤（STS）是一组异质性的罕见肿瘤，其生物标志物的识别和验证可能会改善临床管理。低分子量（LMW）循环蛋白和蛋白片段的部分是新的潜在生物标志物的丰富来源。为了鉴定对STS早期诊断和预后有用的循环生物标志物，我们使用水凝胶核-壳纳米颗粒分析了53份高级别STS血清，所述水凝胶核-壳纳米颗粒通过尺寸排阻和亲和色谱选择性地捕获LMW蛋白，保护它们免于降解并放大它们的浓度用于质谱检测。22种主要参与炎症和免疫反应的分析物显示出从良性到恶性STS的逐渐增加，与健康对照相比，丰度的相对差异超过50%。其中16例转移性肿瘤高于非转移性肿瘤。Cox回归分析显示乳转铁蛋白（LTF）和补体因子H相关5（CFHR 5）的丰度与转移风险之间存在统计学显著相关性。特别是，CFHR 5与转移风险相关。循环蛋白在转移进展中的作用对于更好地理解STS生物学和患者管理至关重要。
Soft tissue sarcomas (STS) are a heterogeneous group of rare tumors for which identification and validation of biological markers may improve clinical management. The fraction of low-molecular-weight (LMW) circulating proteins and fragments of proteins is a rich source of new potential biomarkers. To identify circulating biomarkers useful for STS early diagnosis and prognosis, we analyzed 53 high-grade STS sera using hydrogel core-shell nanoparticles that selectively entrap LMW proteins by size exclusion and affinity chromatography, protect them from degradation and amplify their concentration for mass spectrometry detection. Twenty-two analytes mostly involved in inflammatory and immunological response, showed a progressive increase from benign to malignant STS with a relative difference in abundance, more than 50% when compared to healthy control. 16 of these were higher in metastatic compared to non-metastatic tumors. Coxs regression analysis revealed a statistical significant association between the abundance of lactotransferrin (LTF) and complement factor H-related 5 (CFHR5) and risk of metastasis. In particular, CFHR5 was associated with the risk of metastasis. The role of circulating proteins involved in metastatic progression will be crucial for a better understanding of STS biology and patient management.