手指汗液作为乳腺癌精准医疗的关键

诸平

据奥地利维也纳医科大学（Medical University of Vienna）2025年1月31日提供的消息,手指汗液作为乳腺癌精准医疗的关键（Finger sweat as the key to precision medicine in breast cancer）。

维也纳大学（University of Vienna）和维也纳医科大学（Medical University of Vienna）的一个研究小组在精准医学领域取得了新的突破：他们开发了一种分析手指汗液代谢谱的创新方法。

一项刚刚发表在著名的EPMA杂志(EPMA Journal)上的初步研究结果表明，这种非侵入性方法可以用于乳腺癌患者，以获取有关病程、治疗效果和个人生活习惯的信息。这将大大提高未来患者的个性化治疗。原文详见：Michael Bolliger, Daniel Wasinger, Julia Brunmair, Gerhard Hagn, Michael Wolf, Karin Preindl, Birgit Reiter, Andrea Bileck, Christopher Gerner, Florian Fitzal, Samuel M. Meier Menches. Mass spectrometry-based analysis of eccrine sweat supports predictive, preventive and personalised medicine in a cohort of breast cancer patients in Austria. EPMA Journal, 2025. DOI: 10.1007/s13167-025-00396-6. Published: 31 January 2025.

参与此项研究的有来自奥地利维也纳医科大学{Department of General Surgery (Division of Visceral Surgery), Medical University of Vienna, Waehringer Guertel 18-20, Vienna, Austria; Department of Laboratory Medicine, Medical University of Vienna, Waehringer Guertel 18–20, Vienna, Austria}、奥地利维也纳的圣弗朗西斯医院（Department of Surgery, St. Francis Hospital, Nikolsdorfergasse 32, Vienna, Austria）、奥地利维也纳大学（Faculty of Chemistry, Department of Analytical Chemistry, University of Vienna, Waehringer Str. 38, Vienna, Austria；Vienna Doctoral School in Chemistry, University of Vienna, Waehringer Str. 38-42, Vienna, Austria; Faculty of Chemistry, Institute of Inorganic Chemistry, University of Vienna, Waehringer Str. 38, Vienna, Austria)、维也纳大学和维也纳医科大学联合代谢组研究所（Joint Metabolome Facility, University of Vienna and Medical University Vienna, Waehringer Str. 38, Vienna, Austria）、奥地利维也纳哈努施医院（Department of Surgery and Vascular Surgery, Hanusch Hospital, Heinrich-Collin-Str. 30, Vienna, Austria）的研究人员。

手指汗液是一种特别“珍贵的液滴”，因为它含有来自组织液（在细胞之间循环）的分子，否则很难接近，并且手指作为许多治疗剂的作用部位具有重要的医学意义。然而，到目前为止，直接分析这种液体的各种参数一直很困难——维也纳大学和维也纳医科大学的联合代谢组研究所的科学家们现在已经取得了巨大的成功。他们开发了一种分析手指汗液的创新方法：完全无痛和非侵入性，极少量的汗液就足够了，并提供了对个人代谢谱的惊人精确的见解。

收集简单，分析准确（Simple collection and precise analysis）

上述论文的通讯作者、此项目的共同研究负责人、维也纳大学分析化学研究所（Institute of Analytical Chemistry at the University of Vienna）的塞缪尔·梅尔-门彻斯（Samuel M. Meier Menches）解释说：“我们的程序对病人来说非常简单：他们在拇指和食指之间拿着一张湿润的特殊纸，收集足以进行分析的微量汗水即可。人们可以很容易地自己做到这一点，而不会受到不愉快的、侵入性的手术的压力，而且这些手术还必须由医疗专业人员进行操作。”然后用质谱法分析手指汗液的成分。这不仅可以检测重要的代谢产物，还可以检测药物管理或生活方式因素，如吸烟习惯等。

首次临床应用（In clinical use for the first time）

目前，这种新的分析方法已首次在临床上用于乳腺癌的生物监测，并在第一化疗阶段的癌症患者中进行了彻底的测试。研究小组能够证明，患者的手指汗液反映了肿瘤的全身影响。除了能够单独跟踪环磷酰胺（cyclophosphamide）和昂丹司琼（ondansetron）等药物的水平和疗效外，还确定了肿瘤肿块引起的代谢谱的显著变化。这种方法可以实现疾病进展的长期生物监测，可以进行非侵入性和分散的监测。“我们能够证明，这种类型的分析可以精确监测乳腺癌的治疗反应和代谢变化，而不必不断地从患者身上采集血液样本，”来自维也纳医科大学普通外科（MedUni Vienna’s Department of General Surgery）的上述论文的第一作者迈克尔·博利格（Michael Bolliger）补充说。

精准医疗的前景（Prospects for precision medicine）

结果表明，手指汗液分析是一种可行的替代侵入性血液测试的方法，可以显著推进精准医疗。

在计划的后续项目中，试点研究将扩展到更大的患者群体，以确认迄今为止的结果。“这项技术仍处于发展阶段，但进一步的研究将会评估其在日常临床实践中的潜力，”维也纳哈努施医院乳房重建的联合研究负责人（Head of Breast Reconstruction at Hanusch Hospital in Vienna）、此项研究的共同负责人弗洛里安·菲茨尔（Florian Fitzal）解释说。研究人员相信，他们的方法将彻底改变获得精确诊断和量身定制治疗的途径。

上述介绍仅供参考，欲了解更多信息敬请注意浏览原文和相关报道。

Abstract

Objective

Metabolomics measurements of eccrine sweat may provide novel and relevant biomedical information to support predictive, preventive and personalised medicine (3PM). However, only limited data is available regarding metabolic alterations accompanying chemotherapy of breast cancer patients related to residual cancer burden (RCB) or therapy response. Here, we have applied Metabo-Tip, a non-invasive metabolomics assay based on the analysis of eccrine sweat from the fingertips, to investigate the feasibility of such an approach, especially with respect to drug monitoring, assessing lifestyle parameters and stratification of breast cancer patients.

Methods

Eccrine sweat samples were collected from breast cancer patients (n=9) during the first cycle of neoadjuvant chemotherapy at four time points in this proof-of-concept study at a Tertiary University Hospital. Metabolites in eccrine sweat were analysed using mass spectrometry. Blood plasma samples from the same timepoints were also collected and analysed using a validated targeted metabolomics kit, in addition to proteomics and fatty acids/oxylipin analysis.

Results

A total of 247 exogenous small molecules and endogenous metabolites were identified in eccrine sweat of the breast cancer patients. Cyclophosphamide and ondansetron were successfully detected and monitored in eccrine sweat of individual patients and accurately reflected the administration schedule. The non-essential amino acids asparagine, serine and proline, as well as ornithine were significantly regulated in eccrine sweat and blood plasma over the therapy cycle. However, their distinct time-dependent profiles indicated compartment-specific distributions. Indeed, the metabolite composition of eccrine sweat seems to largely resemble the composition of the interstitial fluid. Plasma proteins and fatty acids/oxylipins were not affected by the first treatment cycle. Individual smoking habit was revealed by the simultaneous detection of nicotine and its primary metabolite cotinine in eccrine sweat. Stratification according to RCB revealed pronounced differences in the metabolic composition of eccrine sweat in these patients at baseline, e.g., essential amino acids, possibly due to the systemic contribution of breast cancer and its impact on metabolic turnover.

Conclusion

Mass spectrometry-based analysis of metabolites from eccrine sweat of breast cancer patients successfully qualified lifestyle parameters for risk assessment and allowed us to monitor drug treatment and systemic response to therapy. Moreover, eccrine sweat revealed a potentially predictive metabolic pattern stratifying patients by the extent of the metabolic activity of breast cancer tissue at baseline. Eccrine sweat is derived from the otherwise hardly accessible interstitial fluid and, thus, opens up a new dimension for biomonitoring of breast cancer in secondary and tertiary care. The simple sample collection without the need for trained personnel could also enable decentralised long-term biomonitoring to assess stable disease or disease progression. Eccrine sweat analysis may indeed significantly advance 3PM for the benefit of breast cancer patients.