Specific Urinary Metabolites in Malignant Melanoma

Abstract

Background and objectives: Melanin, which has a confirmed role in melanoma cell behaviour, is formed in the process of melanogenesis and is synthesized from tryptophan, L-tyrosine and their metabolites. All these metabolites are easily detectable by chromatography in urine. Materials and Methods: Urine samples of 133 individuals (82 malignant melanoma patients and 51 healthy controls) were analysed by reversed-phase high-performance liquid chromatography (RP-HPLC). The diagnosis of malignant melanoma was confirmed histologically. Results: Chromatograms of melanoma patients showed increased levels of 5,6-dihydroxyindole-2-carboxylic acid, vanilmandelic acid, homovanilic acid, tryptophan, 5-hydroxyindole-3-acetic acid, and indoxyl sulphate compared to healthy controls. Concentration of indoxyl sulphate, homovanilic acid and tryptophan were significantly increased even in the low clinical stage 0 of the disease (indoxyl sulphate, homovanilic acid and tryptophan in patients with clinical stage 0 vs. controls expressed as medium/ interquartile range in µmol/mmol creatinine: 28.37/15.30 vs. 5.00/6.91; 47.97/33.08 vs. 7.33/21.25; and 16.38/15.98 vs. 3.46/6.22, respectively). Conclusions: HPLC detection of metabolites of L-tyrosine and tryptophan in the urine of melanoma patients may play a significant role in diagnostics as well as a therapeutic strategy of melanoma cancer.

Significance of 5-S-Cysteinyldopa as a Marker for Melanoma

“…Valko-Rokytovská et al suggested that the following urinary metabolites can significantly contribute to the detection of melanoma: DHICA, vanilmandelic acid, homovanilic acid, tryptophan, 5-hydroxyindole-3-acetic acid and indoxyl sulphate [73]. However, the indole derivatives 6H5MI2C and 5H6MI2C are considered to be less effective than 5SCD because they are very unstable, and the analytical method needed to detect them is complicated.…”

Strong Dependence between Tryptophan-Related Fluorescence of Urine and Malignant Melanoma

“…[ 29 ], but also small molecules that are precursors of eumelanin and pheomelanin, such as 5-S cysteinyldopa, 6-hydroxy-5-methoxyindole-2-carboxylic acid, 5,6-dihydroxyindole, 5,6-dihydroxyindole-2-carboxylic acid [ 30 , 31 ]. Other melanoma-related derivatives of amino acids phenylalanine and tryptophan are also described, such as vanilmandelic acid, homovanilic acid, 5-hydroxyindole-3-acetic acid and indoxyl sulfate [ 18 ]. Many of these mentioned small molecules fluoresce naturally and are also present in urine.…”

“…Some studies have shown that, in addition to tyrosine, tryptophan and some of its metabolites are also involved in melanin biosynthesis [ 16 , 17 , 18 ]. Serotonin and its metabolite 5-hydroxyindole-3-acetic acid (5-HIAA) occurring in urine act as specific tumor markers, and increased production of 5-HIAA have been documented in human epidermal keratinocytes and melanoma cells [ 17 ].…”

Liquid-Chromatographic Methods for Carboxylic Acids in Biological Samples

“…Indole derivatives and glycated tryptophan in rat plasma, mouse plasma, and brain were analyzed with fluorescence detection [40,41], and those in livestock urine and plasma were analyzed with LC-MS to monitor their health [42][43][44]. Valko-Rokytovska et al quantified melanin-related carboxylic compounds in human urine by HPLC-UV for the diagnosis of melanoma cancer, and found that homovanilic acid and tryptophan levels increased in the initial clinical stage of the disease [45]. Catechol-bearing carboxylic acids were separated by ion exchange chromatography, followed by derivatization with ethylenediamine and fluorescence detection [46].…”