Metabolomics of primary cutaneous melanoma and matched adjacent extratumoral microenvironment

Taylor, Nicholas; Gaynanova, Irina; Eschrich, Steven A.; Welsh, Eric A.; Garrett, Timothy J.; Beecher, Chris; Sharma, Ritin; Koomen, John M.; Smalley, Keiran S.M.; Messina, Jane L.; Kanetsky, Peter A.

doi:10.1371/journal.pone.0240849

Cited by 15 publications

(8 citation statements)

References 61 publications

(51 reference statements)

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“…SPRR1B gene enrichment analysis showed that the high expression group enriched the first ascorbic acid and alginate pathway, and it was found that the metabolites of ascorbic acid and alginate were different before and after skin melanoma metastasis, which may be related to the metastasis progress ( 54 ). The high expression of SPRR1B has a poor prognosis and plays an important role in the prognostic model, which shows its potential as a good prognostic marker for cutaneous melanoma.…”

Section: Discussionmentioning

confidence: 99%

Integration Analysis of m6A Related Genes in Skin Cutaneous Melanoma and the Biological Function Research of the SPRR1B

et al. 2021

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Melanoma has gradually entered the public view because of its high morbidity and rising prevalence rate, which is a serious threat to human life and health. Recently, N6-methyladenine (m6A) modification has been increasingly confirmed as a potential role in the development of tumogenesis. The purpose of this study is to explore the role and function of m6a-related regulators in the development of melanoma disease at the molecular, cellular and clinical levels through bioinformatics and traditional experiments. We screened and validated differential expression genes (DEGs) in m6A regulators via the GEO, GTEx, TCGA database. The biological processes and signaling pathway involved by DEGs were improved by constructing bioinformational methods such as PPI, GO enrichment, KEGG enrichment, GSEA enrichment, and immune infiltration analysis. And then, we explored the biological function of the key gene, SPRR1B, through cell invasion, migration, infiltration, and tissue chips. The gene IGF2BP3 which was differentially expressed in m6A regulatory factor gene was screened. The results of the enrichment analysis are significantly enriched in the biological processes and pathways of the skin barrier, epidermal differentiation, cytoskeleton, lymphocyte migration and other pathways, pointing to the direction of tumor immunity and tumor metastasis. Tumor immune-related genes YTHDC1, YTHDC2 and ALKBH5 were found. Knock SPRR1B reduction group had a significantly lower invasive ability, the ability to migrate. Nomogram prediction model shows that SPRR1B increased, expressing a worse prognosis. For this purpose, the relationship between m6A regulatory factor and melanoma progression was explored. At the same time, it was found that the abnormal up-regulated expression of SPRR1B before metastasis would lead to poor prognosis of melanoma. SPRR1B promotes the proliferation, invasion and migration of human melanoma cells.

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Section: Discussionmentioning

confidence: 99%

Integration Analysis of m6A Related Genes in Skin Cutaneous Melanoma and the Biological Function Research of the SPRR1B

et al. 2021

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“…Melanomas can be caused by the dysregulation of the enzymatic activity of tyrosinase, an enzyme responsible for the biosynthesis of melanin. Melanogenesis corresponds to the biochemical process involved with the production and distribution of melanin pigment [ 3 , 4 ], and it is modulated by genetic, hormonal, and environmental factors, such as exposure to ultraviolet rays and abnormal hormonal production [ 3 , 5 , 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

Analysis of Kojic Acid Derivatives as Competitive Inhibitors of Tyrosinase: A Molecular Modeling Approach

et al. 2021

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Tyrosinases belong to the functional copper-containing proteins family, and their structure contains two copper atoms, in the active site, which are coordinated by three histidine residues. The biosynthesis of melanin in melanocytes has two stages depending on the actions of the natural substrates L-DOPA and L-tyrosine. The dysregulation of tyrosinase is involved in skin cancer initiation. In the present study, using molecular modeling tools, we analyzed the inhibition activity of tyrosinase activity using kojic acid (KA) derivatives designed from aromatic aldehydes and malononitrile. All derivatives showed conformational affinity to the enzyme active site, and a favorable distance to chelate the copper ion, which is essential for enzyme function. Molecular dynamics simulations revealed that the derivatives formed promising complexes, presenting stable conformations with deviations between 0.2 and 0.35 Å. In addition, the investigated KA derivatives showed favorable binding free energies. The most stable KA derivatives showed the following binding free energies: −17.65 kcal mol−1 (D6), −18.07 kcal mol−1 (D2), −18.13 (D5) kcal mol−1, and −10.31 kcal mol−1 (D4). Our results suggest that these derivatives could be potent competitive inhibitors of the natural substrates of L-DOPA (−12.84 kcal mol−1) and L-tyrosine (−9.04 kcal mol−1) in melanogenesis.

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“…The same group also identified lauric acid and palmitic acid as melanoma-specific volatile metabolites; increased lipid synthesis due to cell growth and proliferation in cancer and increased oxidative stress could explain such findings [ 19 ]. In 2020, Taylor and colleagues performed a metabolomics investigation of primary melanoma, metastatic lesions, and matched extra-tumoral microenvironment (EM) tissues [ 95 ]. Pathway-based results led to the identification of metabolic changes in ascorbate, aldarate, propanoate, tryptophan, histidine, and pyrimidine; such specific alterations were found to be present in both primary and metastatic melanoma but not in EM, therefore suggesting they are crucial in the initiation and/or maintenance of melanoma [ 95 ].…”

Section: Resultsmentioning

confidence: 99%

Current Knowledge in Skin Metabolomics: Updates from Literature Review

Paganelli

Righi

Tarentini³

et al. 2022

IJMS

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Metabolomic profiling is an emerging field consisting of the measurement of metabolites in a biological system. Since metabolites can vary in relation to different stimuli, specific metabolic patterns can be closely related to a pathological process. In the dermatological setting, skin metabolomics can provide useful biomarkers for the diagnosis, prognosis, and therapy of cutaneous disorders. The main goal of the present review is to present a comprehensive overview of the published studies in skin metabolomics. A search for journal articles focused on skin metabolomics was conducted on the MEDLINE, EMBASE, Cochrane, and Scopus electronic databases. Only research articles with electronically available English full text were taken into consideration. Studies specifically focused on cutaneous microbiomes were also excluded from the present search. A total of 97 papers matched all the research criteria and were therefore considered for the present work. Most of the publications were focused on inflammatory dermatoses and immune-mediated cutaneous disorders. Skin oncology also turned out to be a relevant field in metabolomic research. Only a few papers were focused on infectious diseases and rarer genetic disorders. All the major metabolomic alterations published so far in the dermatological setting are described extensively in this review.

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Metabolomics of primary cutaneous melanoma and matched adjacent extratumoral microenvironment

Cited by 15 publications

References 61 publications

Integration Analysis of m6A Related Genes in Skin Cutaneous Melanoma and the Biological Function Research of the SPRR1B

Integration Analysis of m6A Related Genes in Skin Cutaneous Melanoma and the Biological Function Research of the SPRR1B

Analysis of Kojic Acid Derivatives as Competitive Inhibitors of Tyrosinase: A Molecular Modeling Approach

Current Knowledge in Skin Metabolomics: Updates from Literature Review

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