Plasma tryptophan pathway metabolites quantified by liquid chromatography-tandem mass spectrometry as biomarkers in neuroendocrine tumor patients

IF 3.3 4区 医学 Q2 ENDOCRINOLOGY & METABOLISM
S. U. Johansen, T. Hansen, A. Nordborg, R. Meyer, R. Goll, J. Florholmen, E. Jensen
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引用次数: 0

Abstract

A good and accessible biomarker is of great clinical value in neuroendocrine tumor (NET) patients, especially considering its frequently indolent nature and long-term follow-up. Plasma chromogranin A (CgA) and 5-hydroxyindoleacetic acid (5-HIAA) are currently used as biomarkers in NET, but their sensitivity and specificity are restricted. 5-HIAA is the main metabolite of serotonin, an important neurotransmitter of the tryptophan pathway. The aim of this study is to estabish a sensitive and accurate method for the quantification of tryptophan pathway metabolites in plasma. We further aimed to evaluate its utility as a clinical tool in NET disease. We obtained plasma samples from NET patients and healthy controls recruited from the University Hospital of North Norway, Tromsø. Samples were analyzed by liquid chromatography-tandem mass spectrometry (LC–MS/MS), and eight metabolites of the tryptophan pathway were quantified. We included 130 NET patients (72/130 small intestinal [SI] NET, 35/130 pancreatic NET, 23/130 other origin) and 20 healthy controls. In the SI-NET group, 26/72 patients presented with symptoms of carcinoid syndrome (CS). We found that combining tryptophan metabolites into a serotonin/kynurenine pathway ratio improved diagnostic sensitivity (92.3%) and specificity (100%) in detecting CS patients from healthy controls compared with plasma 5-HIAA alone (sensitivity 84.6%/specificity 100%). Further, a clinical marker based on the combination of plasma serotonin, 5-HIAA, and 5OH-tryptophan, increased diagnostic capacity identifying NET patients with metastasized disease from healthy controls compared with singular plasma 5-HIAA, serotonin, or CgA. In addition, this marker was positive in 61% of curatively operated SI-NET patients compared with only 10% of healthy controls (p < .001). Our results indicate that simultaneous quantification of several tryptophan metabolites in plasma, using LC–MS/MS, may represent a clinically useful diagnostic tool in NET disease.

Abstract Image

用液相色谱-串联质谱法量化神经内分泌肿瘤患者血浆色氨酸途径代谢物作为生物标记物。
对于神经内分泌肿瘤(NET)患者来说,一个好的、容易获得的生物标记物具有重要的临床价值,特别是考虑到其经常具有不显性和长期随访的特点。目前,血浆嗜铬粒蛋白 A(CgA)和 5-羟基吲哚乙酸(5-HIAA)被用作 NET 的生物标记物,但它们的敏感性和特异性受到限制。5-HIAA 是血清素的主要代谢产物,而血清素是色氨酸通路的一种重要神经递质。本研究旨在建立一种灵敏、准确的方法来定量检测血浆中的色氨酸通路代谢物。我们还旨在评估该方法作为 NET 疾病临床工具的实用性。我们从位于特罗姆瑟的北挪威大学医院获取了NET患者和健康对照者的血浆样本。样本采用液相色谱-串联质谱法(LC-MS/MS)进行分析,并对色氨酸途径的八种代谢物进行了定量。研究对象包括 130 名 NET 患者(72/130 名小肠 [SI] NET 患者,35/130 名胰腺 NET 患者,23/130 名其他来源的 NET 患者)和 20 名健康对照组。在SI-NET组中,26/72的患者出现类癌综合征(CS)症状。我们发现,与单用血浆 5-HIAA 相比(灵敏度 84.6%/特异度 100%),将色氨酸代谢物与血清素/犬尿氨酸通路比值相结合可提高从健康对照组中检测 CS 患者的诊断灵敏度(92.3%)和特异度(100%)。此外,与单一的血浆 5-HIAA、5-羟色胺或 CgA 相比,基于血浆 5-羟色胺、5-HIAA 和 5OH- 色氨酸组合的临床标记物提高了从健康对照组中识别有转移疾病的 NET 患者的诊断能力。此外,在 61% 的接受根治性手术的 SI-NET 患者中,该标记物呈阳性,而在健康对照组中,该标记物的阳性率仅为 10%(P<0.05)。
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来源期刊
Journal of Neuroendocrinology
Journal of Neuroendocrinology 医学-内分泌学与代谢
CiteScore
6.40
自引率
6.20%
发文量
137
审稿时长
4-8 weeks
期刊介绍: Journal of Neuroendocrinology provides the principal international focus for the newest ideas in classical neuroendocrinology and its expanding interface with the regulation of behavioural, cognitive, developmental, degenerative and metabolic processes. Through the rapid publication of original manuscripts and provocative review articles, it provides essential reading for basic scientists and clinicians researching in this rapidly expanding field. In determining content, the primary considerations are excellence, relevance and novelty. While Journal of Neuroendocrinology reflects the broad scientific and clinical interests of the BSN membership, the editorial team, led by Professor Julian Mercer, ensures that the journal’s ethos, authorship, content and purpose are those expected of a leading international publication.
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