Abstract
The tryptophan to kynurenine ratio (Trp/Kyn) has been proposed as a cancer biomarker. Non-invasive topical sampling of Trp/Kyn can therefore serve as a promising concept for skin cancer diagnostics. By performing in vitro pig skin permeability studies, we conclude that non-invasive topical sampling of Trp and Kyn is feasible. We explore the influence of different experimental conditions, which are relevant for the clinical in vivo setting, such as pH variations, sampling time, and microbial degradation of Trp and Kyn. The permeabilities of Trp and Kyn are overall similar. However, the permeated Trp/Kyn ratio is generally higher than unity due to endogenous Trp, which should be taken into account to obtain a non-biased Trp/Kyn ratio accurately reflecting systemic concentrations. Additionally, prolonged sampling time is associated with bacterial Trp and Kyn degradation and should be considered in a clinical setting. Finally, the experimental results are supported by the four permeation pathways model, predicting that the hydrophilic Trp and Kyn molecules mainly permeate through lipid defects (i.e., the porous pathway). However, the hydrophobic indole ring of Trp is suggested to result in a small but noticeable relative increase of Trp diffusion via pathways across the SC lipid lamellae, while the shunt pathway is proposed to slightly favor permeation of Kyn relative to Trp.
Highlights
The tryptophan to kynurenine ratio (Trp/Kyn) has been proposed as a cancer biomarker
Despite an increasing number of molecules recognized as skin cancer biomarkers, e.g. cytokines such as interleukin 6 (IL-6) or interferon gamma (IFNγ)[5], enzyme indoleamine-2,3-dioxygenase[6], v-raf murine sarcoma viral oncogene homologue B1 (BRAF) gene mutations[7], their applications are limited in terms of non-invasive diagnostics
To enable sampling and analysis of the potential skin cancer biomarker, i.e., the Trp/Kyn ratio, from the skin surface, it is required to characterize how the Trp/Kyn ratio on the surface of the skin correlates with the ratio existing in the viable epidermis
Summary
The tryptophan to kynurenine ratio (Trp/Kyn) has been proposed as a cancer biomarker. Despite an increasing number of molecules recognized as skin cancer biomarkers, e.g. cytokines such as interleukin 6 (IL-6) or interferon gamma (IFNγ)[5], enzyme indoleamine-2,3-dioxygenase[6], v-raf murine sarcoma viral oncogene homologue B1 (BRAF) gene mutations[7], their applications are limited in terms of non-invasive diagnostics. In particular for various skin cancers, since both Trp and Kyn are low molecular weight substances that are expected to diffuse relatively unrestricted across the skin barrier tissue and have sufficiently high skin surface concentrations for non-invasive topical sampling of the Trp/Kyn ratio. It is crucial to characterize the skin permeabilities of Trp and Kyn at different conditions in order to evaluate if the Trp/Kyn ratio can be monitored non-invasively from samples collected from the skin surface
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