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黑色素瘤及相邻非病变皮肤中色氨酸和犬尿氨酸与苯丙氨酸和酪氨酸的非侵入性胶带采样:一项初步研究。

Non-invasive tape sampling of tryptophan and kynurenine in relation to phenylalanine and tyrosine from melanoma and adjacent non-lesional skin: A pilot study.

作者信息

Jankovskaja Skaidre, Spégel Peter, Nielsen Kari, Björklund Sebastian, Bost Jeremy, Engblom Johan, Christensen Gustav, Rogova Oksana, Morin Maxim, Haedersdal Merete, Malmsten Martin, Anderson Chris D, Ruzgas Tautgirdas

机构信息

Department of Biomedical Science, Malmö University, Sweden.

Biofilms Research Centre for Biointerfaces, Malmö University, Sweden.

出版信息

PLoS One. 2025 Jun 24;20(6):e0326457. doi: 10.1371/journal.pone.0326457. eCollection 2025.

Abstract

PURPOSE

To evade immunosurveillance many cancers convert tryptophan (Trp) into kynurenine (Kyn), which induces immunotolerance and suppresses immune responses. Elevated Kyn amounts have been found in blood from patients with cutaneous melanoma. This study aimed to investigate whether higher Kyn abundance and lower Trp abundance can be detected on the surface of cutaneous melanoma lesions compared with adjacent non-lesional skin.

METHODS

Sixteen patients with suspected melanomas were enrolled in this study. All lesions were excised and histopathologically diagnosed: 7 lesions were diagnosed as invasive malignant melanomas (MM), 6 as melanomas in situ (MIS), and 3 as benign lesions (BL). Non-invasive metabolite sampling was performed by tape stripping of suspected skin lesions and adjacent healthy non-lesional (NL) skin. Trp, Kyn, tyrosine (Tyr), and phenylalanine (Phe) were quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Electrical impedance spectroscopy (EIS) measurements were conducted to assess skin barrier integrity.

RESULTS

Levels of all metabolites, Tyr (x6), Phe (x6), Trp (x5), and Kyn (x3), were significantly higher in MM lesions compared with adjacent NL skin, resulting in an elevated Trp/Kyn ratio. Trp levels increased less than Phe and Tyr levels, suggesting a potential increase in Trp depletion. Skin resistance in MM lesions was half that of NL skin. No differences were observed between MIS or BL and NL skin.

CONCLUSIONS

Non-invasive skin sampling revealed elevated Tyr, Phe, Trp and Kyn levels in MM skin, which is likely the result of compromised skin barrier at this stage of cutaneous melanoma.

摘要

目的

为了逃避免疫监视,许多癌症将色氨酸(Trp)转化为犬尿氨酸(Kyn),后者可诱导免疫耐受并抑制免疫反应。在皮肤黑色素瘤患者的血液中发现犬尿氨酸含量升高。本研究旨在调查与相邻的非病变皮肤相比,在皮肤黑色素瘤病变表面是否能检测到更高的犬尿氨酸丰度和更低的色氨酸丰度。

方法

本研究纳入了16例疑似黑色素瘤患者。所有病变均被切除并进行组织病理学诊断:7例病变被诊断为侵袭性恶性黑色素瘤(MM),6例为原位黑色素瘤(MIS),3例为良性病变(BL)。通过胶带剥离疑似皮肤病变和相邻的健康非病变(NL)皮肤进行非侵入性代谢物采样。采用液相色谱 - 串联质谱法(LC-MS/MS)对色氨酸、犬尿氨酸、酪氨酸(Tyr)和苯丙氨酸(Phe)进行定量分析。进行电阻抗光谱(EIS)测量以评估皮肤屏障完整性。

结果

与相邻的NL皮肤相比,MM病变中所有代谢物(酪氨酸(x6)、苯丙氨酸(x6)、色氨酸(x5)和犬尿氨酸(x3))的水平均显著升高,导致色氨酸/犬尿氨酸比值升高。色氨酸水平的升高低于苯丙氨酸和酪氨酸水平,表明色氨酸消耗可能增加。MM病变中的皮肤电阻是NL皮肤的一半。MIS或BL与NL皮肤之间未观察到差异。

结论

非侵入性皮肤采样显示MM皮肤中酪氨酸、苯丙氨酸、色氨酸和犬尿氨酸水平升高,这可能是皮肤黑色素瘤此阶段皮肤屏障受损的结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eff2/12186910/c6496dcfb01f/pone.0326457.g001.jpg

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