Novel serum metabolomics‐based approach by gas chromatography/triple quadrupole mass spectrometry for detection of human skin cancers: Candidate biomarkers

Abstract

Skin cancer incidence rates are continuing to rise; however, if detected at an early stage, they can be cured with minimally invasive treatment. Therefore, the identification of novel and robust biomarkers for the early detection of skin cancer is required to improve the quality of life of the patient after treatment. In the present study, we aimed to identify novel biomarkers of skin cancers. We carried out serum metabolomics using gas chromatography/triple quadrupole mass spectrometry for two types of skin cancer: squamous cell carcinoma and melanoma. The changes in the expression of metabolites compared with healthy volunteers were analyzed by principal component analysis. Among all 118 metabolites, 27 in patients with squamous cell carcinoma and 33 in patients with melanoma showed significant changes in comparison with healthy volunteers. Principal component analysis showed that both skin cancer groups could be distinguished from the healthy volunteers group. We further investigated the specific metabolites most useful for these distinctions. In the squamous cell carcinoma group, these metabolites were glycerol, 4-hydroxybenzoic acid, sebacic acid, fucose and suberic acid. In the melanoma group, these metabolites were glutamic acid, sebacic acid, suberic acid, 4-hydroxybenzoic acid and phenylalanine. The present study identified several metabolites that were distinct for certain skin cancer types, which could potentially be used as diagnostic biomarkers leading to novel clinical management strategies.

Current Knowledge in Skin Metabolomics: Updates from Literature Review

“…Most of the available data are based on cutaneous sample metabolomic assessment, with only one publication focusing on serum metabolites [ 41 ].…”

“…Several authors already reported on metabolomics as a useful tool for discriminating different types of cutaneous cancer [ 41 , 74 ]. Specific serum metabolites were found to differ between patients with squamous cell carcinoma (SCC) and melanoma, and both skin cancer groups could be distinguished from healthy controls [ 41 ]. SCC-specific metabolites included glycerol, 4-hydroxybenzoic acid, sebacic acid, fucose, and suberic acid.…”

High-throughput metabolome comparison of cutaneous squamous cell carcinoma, basal cell carcinoma, and healthy skin with e-biopsy sampling

“…The analysis of molecular information obtained from specimens collected with this method has successfully differentiated between healthy and cancerous skin tissues [10][11][12] . Combined with highthroughput analytics that have demonstrated their ability to identify genes, proteins, lipids, and metabolites of cSCC and BCC [13][14][15][16][17][18][19][20] , e-biopsy is a promising direction for analysis of water-soluble molecules of skin cancers. E-biopsy broadens the spectrum of capabilities of handheld devices in cancer diagnostics and differs from tools such as the iKnife 21,22 and MasSpec Pen 23,24 which have been designed for intraoperative use and require real-time connection to a mass spectrometer.…”

“…Metabolomic analyses of cSCC and BCC have previously reported differences in cancerous tissues compared to healthy [14][15][16]18,19 . These reports have used a variety of analysis methods such as highresolution magic angle spinning (HR-MAS) 1H nuclear magnetic resonance (NMR) spectroscopy 14 , liquid chromatography tandem mass spectrometry (LC-MS-MS) 15 , triple-quadrupole MS (QqQMS) 16 , ultraperformance LC coupled to a time-of-flight tandem MS (UPLC-TOF-MS/MS) 18 , and 1H NMR spectroscopy 19 , and have identified 9, 27, 27, 181, and 8 significant metabolites, respectively. These studies used both tissue 14,15,18,19 and serum 16 samples.…”

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“…In this study, 20-COOH-leukotriene E4 was up-regulated in cancer tissues after chemotherapy, which may be associated with enhanced γ-GGT activity after chemotherapy, leading to increased synthesis, consistent with elevated serum γ-GGT in post-chemotherapy patients. Sebacic acid is a medium chain acyl-coenzyme A dehydrogenase (ACADM), metabolite that is present in a variety of tumors, such as squamous cell carcinoma of the skin and melanoma (Fukumoto et al, 2017;Li et al, 2019). Lack of ACADM indirectly leads to the increase of sebacic acid in patients after chemotherapy.…”