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挥发物组学——作为潜在肿瘤标志物的挥发性有机代谢物(VOM)在头颈部鳞状细胞癌(HNSCC)患者中的研究。

The volatilome - investigation of volatile organic metabolites (VOM) as potential tumor markers in patients with head and neck squamous cell carcinoma (HNSCC).

机构信息

Institute of Hygiene, Hospital Hygiene and Environmental Medicine, University Hospital Leipzig, Johannisallee 34, 04103, Leipzig, Germany.

Institute of Environmental Medicine and Hygiene, Faculty of Medicine, University of Leipzig, Liebigstr. 27, 04103, Leipzig, Germany.

出版信息

J Otolaryngol Head Neck Surg. 2018 Jul 3;47(1):42. doi: 10.1186/s40463-018-0288-5.

Abstract

BACKGROUND

Different organisms such as bacteria, molds and humans produce and release a relative unknown class of metabolites which are responsible for the individual olfactory pattern. These volatile organic metabolites (VOM) represent a kind of biosignature that reflects the sum of all multifactorial influences, including genetics, environmental factors, nutritional and disease status. As a result of pathological processes the individual body odor can be influenced by newly produced or altered compositions of the VOM. Until now, human VOM have been detected in various body media, such as on the skin, in the exhaled air as well as in body fluids such as saliva, mother's milk, sweat, blood and urine.

METHODS

In this retrospective case-control study urinary VOM of 53 therapy-naive patients with head and neck squamous cell carcinoma (HNSCC) and 82 healthy controls were semi-quantified by headspace solid-phase micro extraction (SPME) gas chromatography (GC) mass spectrometry (MS). At first, the procedure was optimized in respect to the extraction parameters. By using Student's t-test significant differences in the VOM pattern with the corresponding p-values were obtained. For multivariate metabolite pattern recognition the hierarchical cluster analysis by Ward was applied, followed by the supervised partial least squares-discriminant analysis (PLS-DA).

RESULTS

In total 81 VOMs could identified in the urine samples of all study participants, of which 25 were significantly increased and of which were 10 significantly reduced in HNSCC-patients compared to the controls. In addition, the multivariate statistics confirmed that on the basis of the renal excreted pattern of the volatile metabolites a high discrimination can be carried out between patients with a tumor in the head and neck region and controls. The substance group of the saturated, unbranched aldehydes makes a substantial contribution in this context.

CONCLUSIONS

The systematic pattern analysis of urinary VOMs appears to have potential clinical application as a diagnostic tool for cancer, especially HNSCC.

摘要

背景

不同的生物体,如细菌、霉菌和人类,会产生和释放一类相对未知的代谢物,这些代谢物负责个体的气味模式。这些挥发性有机代谢物(VOM)代表了一种生物特征,反映了包括遗传、环境因素、营养和疾病状态在内的多种多因素影响的总和。由于病理过程,个体的体味可能会受到 VOM 中新产生或改变的成分的影响。到目前为止,已经在各种身体介质中检测到人类 VOM,例如皮肤、呼出的空气中,以及唾液、母乳、汗液、血液和尿液等体液中。

方法

在这项回顾性病例对照研究中,通过顶空固相微萃取(SPME)气相色谱(GC)质谱(MS)对半定量了 53 名未经治疗的头颈部鳞状细胞癌(HNSCC)患者和 82 名健康对照者的尿液 VOM。首先,优化了提取参数的程序。通过使用学生 t 检验,获得了具有相应 p 值的 VOM 模式的显著差异。为了进行多元代谢物模式识别,应用了 Ward 的层次聚类分析,然后是有监督的偏最小二乘判别分析(PLS-DA)。

结果

在所有研究参与者的尿液样本中总共鉴定出 81 种 VOM,其中 25 种在 HNSCC 患者中显著增加,10 种显著减少。此外,多元统计学证实,基于挥发性代谢物的肾脏排泄模式,可以对头颈部肿瘤患者和对照组进行高度区分。在这方面,饱和无支链醛物质组做出了实质性贡献。

结论

尿液 VOM 的系统模式分析似乎具有作为癌症,特别是 HNSCC 的诊断工具的潜在临床应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e44f/6029417/3a5a2de7fb69/40463_2018_288_Fig1_HTML.jpg

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