Becker Roland
Bundesanstalt für Materialforschung und -prüfung (BAM), Berlin, Germany.
Med Hypotheses. 2020 Oct;143:110060. doi: 10.1016/j.mehy.2020.110060. Epub 2020 Jul 1.
In recent years numerous reports have highlighted the options of chemical breath analysis with regard to non-invasive cancer detection. Certain volatile organic compounds (VOC) supposedly present in higher amounts or in characteristic patterns have been suggested as potential biomarkers. However, so far no clinical application based on a specific set of compounds appears to exist. Numerous reports on the capability of sniffer dogs and sensor arrays or electronic noses to distinguish breath of cancer patients and healthy controls supports the concept of genuine cancer-related volatile profiles. However, the actual compounds responsible for the scent are completely unknown and there is no correlation with the potential biomarkers suggested on basis of chemical trace analysis. It is outlined that specific features connected with the VOC analysis in breath - namely small concentrations of volatiles, interfering background concentrations, considerable sampling effort and sample instability, impracticability regarding routine application - stand in the way of substantial progress. The underlying chemical-analytical challenge can only be met considering the severe susceptibility of VOC determination to these adverse conditions. Therefore, the attention is drawn to the needs for appropriate quality assurance/quality control as the most important feature for the reliable quantification of volatiles present in trace concentration. Consequently, the advantages of urine as an alternative matrix for volatile biomarker search in the context of diagnosing lung and other cancers are outlined with specific focus on quality assurance and practicability in clinical chemistry. The headspace over urine samples as the VOC source allows adapting gas chromatographical procedures well-established in water analysis. Foremost, the selection of urine over breath as non-invasive matrix should provide considerably more resilience to adverse effects during sampling and analysis. The most important advantage of urine over breath is seen in the option to partition, dispense, mix, spike, store, and thus to dispatch taylor-made urine samples on demand for quality control measures. Although it is still open at this point if cancer diagnosis supported by non-invasively sampled VOC profiles will ultimately reach clinical application the advantages of urine over breath should significantly facilitate urgently required steps beyond the current proof-of-concept stage and towards standardisation.
近年来，大量报告强调了化学呼气分析在非侵入性癌症检测方面的应用前景。某些挥发性有机化合物（VOC）被认为在癌症患者体内含量更高或呈现出特定模式，有望成为潜在的生物标志物。然而，目前似乎尚未出现基于特定化合物组合的临床应用。众多关于嗅探犬、传感器阵列或电子鼻区分癌症患者和健康对照者呼吸能力的报告，支持了存在与癌症相关的独特挥发性特征这一概念。然而，产生气味的实际化合物完全未知，且与基于化学痕量分析提出的潜在生物标志物没有关联。据概述，与呼气中VOC分析相关的特定问题——即挥发性物质浓度低、背景浓度干扰、采样工作量大以及样品不稳定，在常规应用中不实用——阻碍了实质性进展。鉴于VOC测定对这些不利条件极为敏感，只有应对潜在的化学分析挑战，才能取得进展。因此，应关注适当质量保证/质量控制的必要性，这是可靠定量痕量挥发性物质的最重要特征。因此，本文概述了尿液作为在肺癌和其他癌症诊断中寻找挥发性生物标志物的替代基质的优势，特别关注临床化学中的质量保证和实用性。尿液样品上方的顶空作为VOC来源，使得适用于水分析的成熟气相色谱程序得以应用。最重要的是，选择尿液而非呼气作为非侵入性基质，在采样和分析过程中应能提供更强的抗不利影响能力。尿液相对于呼气的最重要优势在于，可以进行分装、混合、加标、储存，并根据质量控制措施的需要按需调配定制的尿液样本。尽管目前通过非侵入性采样的VOC谱支持癌症诊断最终能否实现临床应用仍未可知，但尿液相对于呼气的优势应能显著推动当前概念验证阶段之后迫切需要的步骤，并朝着标准化方向发展。
