Identification of blood biomarkers in glioblastoma by SWATH mass spectrometry and quantitative targeted absolute proteomics.

Identification of blood biomarkers in glioblastoma by SWATH mass spectrometry and quantitative targeted absolute proteomics.
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DOI:
10.1371/journal.pone.0193799
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发表时间:
2018
期刊:
影响因子:
3.7
通讯作者:
Nakada M
Nakada M
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Miyauchi E;Furuta T;Ohtsuki S;Tachikawa M;Uchida Y;Sabit H;Obuchi W;Baba T;Watanabe M;Terasaki T;Nakada M

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需要血液中的分子生物标志物来帮助胶质母细胞瘤(GBM)的早期诊断和临床评估。在此,为了鉴定GBM患者血浆中的生物标志物候选物,我们使用SWATH质谱分析对GBM患者(n = 14)和健康对照(n = 15)的血浆蛋白质组进行定量比较。通过定量靶向绝对蛋白质组学分析验证了结果。因此,我们鉴定了GBM的8种生物标志物候选物(富含亮氨酸的α-2-糖蛋白(LRG 1)、补体成分C9(C9)、C反应蛋白(CRP)、α-1-抗胰凝乳蛋白酶(SERPINA 3)、载脂蛋白B-100(APOB)、凝溶胶蛋白(GSN)、IG α-1链C区(IGHA 1)和载脂蛋白A-IV(APOA 4))。其中,LRG 1、C9、CRP、GSN、IGHA 1和APOA 4的受试者工作特征曲线下面积值大于0.80。为了研究生物标志物候选物与GBM生物学之间的关系,我们检查了GBM患者中生物标志物候选物的血浆浓度与临床表现(肿瘤大小、无进展生存时间或总生存时间)之间的相关性。LRG 1、CRP和C9的血浆浓度与肿瘤大小呈显著正相关(R2分别为0.534、0.495和0.452)。
Molecular biomarkers in blood are needed to aid the early diagnosis and clinical assessment of glioblastoma (GBM). Here, in order to identify biomarker candidates in plasma of GBM patients, we performed quantitative comparisons of the plasma proteomes of GBM patients (n = 14) and healthy controls (n = 15) using SWATH mass spectrometry analysis. The results were validated by means of quantitative targeted absolute proteomics analysis. As a result, we identified eight biomarker candidates for GBM (leucine-rich alpha-2-glycoprotein (LRG1), complement component C9 (C9), C-reactive protein (CRP), alpha-1-antichymotrypsin (SERPINA3), apolipoprotein B-100 (APOB), gelsolin (GSN), Ig alpha-1 chain C region (IGHA1), and apolipoprotein A-IV (APOA4)). Among them, LRG1, C9, CRP, GSN, IGHA1, and APOA4 gave values of the area under the receiver operating characteristics curve of greater than 0.80. To investigate the relationships between the biomarker candidates and GBM biology, we examined correlations between plasma concentrations of biomarker candidates and clinical presentation (tumor size, progression-free survival time, or overall survival time) in GBM patients. The plasma concentrations of LRG1, CRP, and C9 showed significant positive correlations with tumor size (R2 = 0.534, 0.495, and 0.452, respectively).
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