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采用蛋白质组学分析方法鉴定无疾病乳腺癌患者与癌因性疲乏综合征(CRFS)相关的血浆蛋白。

The identification of plasma proteins associated with cancer-related fatigue syndrome (CRFS) in disease-free breast cancer patients using proteomic analysis.

机构信息

Cancer Research UK and Division of Population Health Sciences and Education, St. George's University of London, London, United Kingdom.

出版信息

J Pain Symptom Manage. 2013 May;45(5):868-74. doi: 10.1016/j.jpainsymman.2012.04.008. Epub 2012 Sep 25.

Abstract

CONTEXT

Cancer-related fatigue syndrome (CRFS) affects a significant minority of women successfully treated for breast cancer, with symptoms lasting up to several years after finishing therapy.

OBJECTIVES

This analysis was conducted to identify plasma proteins associated with CRFS in disease-free breast cancer patients.

METHODS

Women were divided into those meeting the CRFS criteria (cases) and a control group on the basis of a diagnostic interview. Plasma samples were collected from 45 cases and 45 controls. Proteomic analysis was conducted using surface-enhanced laser desorption/ionization, a mass spectrometry (MS) technique. This was followed by further sample processing using one-dimensional gels and trypsin digest for protein identification using liquid chromatography and database searching.

RESULTS

CRFS was associated with a statistically significant increase in the intensity of seven MS spectra. A subsequent search of proteins corresponding to the MS spectra identified four acute phase proteins associated with a nonspecific immune response (serum amyloid A, collectin, and subunits of immunoglobulin G and complement C1Q).

CONCLUSION

These novel results (using a technique not previously used in fatigue research) add further weight to the hypothesis that CRFS may be precipitated and prolonged by a nonspecific sustained inflammatory response. Importantly, this has been identified from a global analysis of plasma, which was conducted with no prior assumptions. Although these results need confirmation, we would suggest that future treatments for CRFS should consider focusing on the modulation of this presumed prolonged immune response.

摘要

背景

癌症相关疲劳综合征(CRFS)影响少数成功接受乳腺癌治疗的女性,症状在完成治疗后可持续数年。

目的

本分析旨在确定与无病乳腺癌患者 CRFS 相关的血浆蛋白。

方法

根据诊断性访谈将女性分为符合 CRFS 标准的病例组和对照组。从 45 例病例和 45 例对照组中采集血浆样本。使用表面增强激光解吸/电离、质谱(MS)技术进行蛋白质组学分析。随后,使用一维凝胶和胰蛋白酶消化进行进一步的样品处理,使用液相色谱和数据库搜索进行蛋白质鉴定。

结果

CRFS 与 MS 谱强度的统计学显著增加相关。随后对对应于 MS 谱的蛋白质进行搜索,鉴定出 4 种与非特异性免疫反应相关的急性期蛋白(血清淀粉样蛋白 A、胶原凝集素和免疫球蛋白 G 和补体 C1Q 的亚单位)。

结论

这些新结果(使用以前未用于疲劳研究的技术)进一步支持了这样的假设,即 CRFS 可能由非特异性持续炎症反应引发和延长。重要的是,这是从对血浆进行的全面分析中得出的,该分析没有预先假设。尽管这些结果需要进一步证实,但我们建议未来治疗 CRFS 应考虑集中于调节这种假定的长期免疫反应。

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