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新型血清肽生物标志物的血清变异性与多发性骨髓瘤的疾病状态相关。

Variability of serum novel serum peptide biomarkers correlates with the disease states of multiple myeloma.

作者信息

Bai Ju, Yang Yun, Wang Jianli, Zhang Lei, Wang Fangxia, He Aili

机构信息

1Department of Hematology, Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, 157 Xiwu Road, Xincheng District, Xi'an, 710004 Shaanxi Province China.

2Department of Clinical Lab, Second Affiliated Hospital, Xi'an Jiaotong University, 157 Xiwu Road, Xi'an, 710004 Shaanxi China.

出版信息

Clin Proteomics. 2019 Apr 23;16:17. doi: 10.1186/s12014-019-9238-0. eCollection 2019.

Abstract

BACKGROUND

The bone marrow microenvironment provides an optimal substrate for multiple myeloma (MM) initiation and progression. The soluble component of MM niche is dynamic with the disease states of MM. We formerly employed proteomic profiling to construct a MM model. Four peptides constituting the model were selected by supervised neural network algorithm (SNN).

METHODS

62 Newly diagnosed (ND) MM and 64 healthy controls (HCs) were picked up for validating the distinguishing capability of the SNN model. Nano-liquid chromatography-electrospray ionization-tandem mass spectrometry was used for peptide identification. MM in different disease states and HCs were choosed for peptides relative intensities comparison. Western blot and ELISA were employed to validate the variability.

RESULTS

The sensitivity and specificity of the independent testing data set for blind validation were 93.55% and 92.19%. The relative intensities of three out of the four peptides were increased in ND and refractory and relapse patients but decreased to that level of HCs in complete remission and very good partial remission patients. Relative intensity of the remaining peptide was negatively associated with MM remission. The peptides sequencing results showed that they were derived from dihydropyrimidinase-like 2, fibrinogen alpha chain, platelet factor 4 and alpha-fetoprotein.

CONCLUSIONS

The potential value of the four peptides in monitoring MM treatment response was arised from their close correlation with MM disease states.

摘要

背景

骨髓微环境为多发性骨髓瘤(MM)的起始和进展提供了最佳底物。MM龛的可溶性成分随MM的疾病状态而动态变化。我们之前采用蛋白质组学分析构建了一个MM模型。通过监督神经网络算法(SNN)选择了构成该模型的四种肽。

方法

选取62例新诊断(ND)MM患者和64例健康对照(HCs)来验证SNN模型的区分能力。采用纳升液相色谱-电喷雾电离-串联质谱法进行肽鉴定。选择不同疾病状态的MM患者和HCs进行肽相对强度比较。采用蛋白质印迹法和酶联免疫吸附测定法验证其变异性。

结果

用于盲法验证的独立测试数据集的灵敏度和特异性分别为93.55%和92.19%。四种肽中的三种在ND、难治性和复发性患者中相对强度增加,但在完全缓解和非常好的部分缓解患者中降至HCs的水平。其余一种肽的相对强度与MM缓解呈负相关。肽测序结果表明,它们分别来源于二氢嘧啶酶样2、纤维蛋白原α链、血小板因子4和甲胎蛋白。

结论

这四种肽在监测MM治疗反应中的潜在价值源于它们与MM疾病状态的密切相关性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/70ca/6477722/1cf467034d0a/12014_2019_9238_Fig1_HTML.jpg

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