早期乳腺癌女性代谢组学与精神神经症状的初步研究
Pilot Study of Metabolomics and Psychoneurological Symptoms in Women With Early Stage Breast Cancer.
作者信息
Lyon Debra E, Starkweather Angela, Yao Yingwei, Garrett Timothy, Kelly Debra Lynch, Menzies Victoria, Dereziński Paweł, Datta Susmita, Kumar Sreelakshmy, Jackson-Cook Colleen
机构信息
1 College of Nursing, University of Florida, Gainesville, FL, USA.
2 School of Nursing, University of Connecticut, Storrs, CT, USA.
出版信息
Biol Res Nurs. 2018 Mar;20(2):227-236. doi: 10.1177/1099800417747411. Epub 2017 Dec 19.
UNLABELLED
Many women with breast cancer experience symptoms of pain, fatigue, and depression, collectively known as psychoneurologic (PN) symptoms, during and after chemotherapy treatment. Evidence that inflammatory dysfunction related to cancer and its treatments contributes to the development and persistence of PN symptoms through several interrelated pathways is accumulating. However, a major limiting factor in more precisely identifying the biological mechanisms underlying these symptoms is the lack of biological measures that represent a holistic spectrum of biological responses. Metabolomics allows for examination of multiple, co-occurring metabolic pathways and provides a systems-level perspective on biological mechanisms that may contribute to PN symptoms.
METHODS
In this pilot study, we performed serum metabolome analysis using liquid chromatography high-resolution mass spectrometry of global and targeted metabolomics from the tryptophan pathway from archived samples from 19 women with early-stage breast cancer. We used paired t tests to compare metabolite concentrations and Pearson's correlation coefficients to examine concomitant changes in metabolite concentrations and PN symptoms before and after chemotherapy.
RESULTS
Levels of pain, fatigue, and depression increased after chemotherapy. Compared with pre-chemotherapy, global metabolites post-chemotherapy were characterized by higher concentrations of acetyl-l-alanine and indoxyl sulfate and lower levels of 5-oxo-l-proline. Targeted analysis indicated significantly higher kynurenine levels and kynurenine/tryptophan ratios post-chemotherapy. Symptoms of pain and fatigue had strong associations with multiple global and several targeted metabolites.
CONCLUSION
Results demonstrated that metabolomics may be useful for elucidating biological mechanisms associated with the development and severity of PN symptoms, specifically pain and fatigue, in women with early-stage breast cancer.
未标注
许多乳腺癌女性在化疗期间及化疗后会出现疼痛、疲劳和抑郁症状，统称为心理神经（PN）症状。越来越多的证据表明，与癌症及其治疗相关的炎症功能障碍通过多种相互关联的途径导致PN症状的发生和持续。然而，更精确地确定这些症状背后生物学机制的一个主要限制因素是缺乏能够代表生物学反应整体谱的生物学测量方法。代谢组学能够检测多种同时发生的代谢途径，并从系统层面提供可能导致PN症状的生物学机制的观点。
方法
在这项初步研究中，我们使用液相色谱高分辨率质谱对来自19名早期乳腺癌女性存档样本中色氨酸途径的整体和靶向代谢组进行血清代谢组分析。我们使用配对t检验比较代谢物浓度，并使用皮尔逊相关系数来检查化疗前后代谢物浓度和PN症状的伴随变化。
结果
化疗后疼痛、疲劳和抑郁水平增加。与化疗前相比，化疗后的整体代谢物特征是乙酰-L-丙氨酸和硫酸吲哚酚浓度较高，而5-氧代-L-脯氨酸水平较低。靶向分析表明化疗后犬尿氨酸水平和犬尿氨酸/色氨酸比值显著升高。疼痛和疲劳症状与多种整体代谢物和几种靶向代谢物有很强的关联。
结论
结果表明，代谢组学可能有助于阐明早期乳腺癌女性中与PN症状（特别是疼痛和疲劳）的发生和严重程度相关的生物学机制。
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