# Skin Cancer Metabolic Profile Assessed by Different Analytical Platforms
## 7 Skin Cancer Metabolomics Using Different Analytical Platforms
### GC-MS Based Skin Cancer Metabolomics
Melanoma samples were positive for malignant melanoma with 0.78 Breslow thickness, and non-neoplastic healthy skin showed signs of solar elastosis [45], which is a degenerative condition associated with chronic damage of the elastic tissue in the dermis layer due to extended sun exposure [47]. Examples of volatile organic compounds found only in melanoma are 1-hexadecene, isopropyl palmitate, ethylene oxide, Bis (2-ethylhexyl!) phthalate, amide formamide, and undecane. Increased metabolism and fatty acid synthesis in melanoma progression led to the formation of palmitic acid derivatives, such as 1-hexadecene and isopropyl palmitate. Moreover, ethylene oxide was detected only in melanoma samples although there are no data that support the formation of endogenous ethylene in animals or humans. 1-aminocyclopropane-1-carboxylate synthase (ACC synthase) is a human enzyme responsible for ethylene synthesis, however, it is allegedly inactive due to mutations of two amino-acid residues within the enzyme's binding site. Thus, it seems that ethylene oxide in melanoma samples is not a primary metabolite. Though intestinal bacteria are supposed to increase ethylene levels, the precursor of ethylene oxide via metabolism and lipid peroxidation, additional studies are needed to explore this mechanism in human skin. The presence of ethylene oxide due to contamination in the punch biopsy device is ruled out because it was not detected in the normal skin samples. Bis(2-ethylhexyl!) phthalate has also been found only in melanoma and not in healthy samples. In general, anthracyclines anticancer drugs are metabolized to phthalate acids through oxidative degeneration, with phthalate esters commonly used as plasticizers. However, our patient did not receive any anthracyclines [46]. Bis (2-ethylhexyl!) phthalate was previously identified to be elevated in melanoma samples compared to both nevi and normal skin [48], so possibilities of contamination and anthracyclines anticancer drugs can be excluded. On the other hand, other volatile organic compounds have been found in both samples but showed 100% enrichment in melanoma samples, compared to healthy skin samples such as 1-hexadecanol, Methyled benzene (Benzene, 1,3,5-trimethyl), and nonanal. 1-Hexadecanol showed a 35-fold increase in melanoma samples, as compared to healthy skin samples, which may reflect the increased synthesis of de novo fatty acid (FA), which is a critical metabolic modification in cancer cells used to synthesize new plasma membrane, considering 1-Hexadecanol as a potential biomarker of melanoma [46]. \begin{table}
\begin{tabular}{l l l l} \hline \hline
**Volatile compounds** & **\%TIC in Melanoma (M)** & **\%TIC in Healthy Skin (S)** & **RATIO M/S** \\ \hline
**1,2-Benzenedicarboxylic acid, diisooctyl ester** & 1.03 & 0.61 & 1.68 \\
**1-Hexadecanol** & 3.29 & 0.09 & 35.90 \\
**2-Ethylehexyl! trans-4-methoxy cinnamate** & 1.02 & 0.78 & 1.31 \\ Benzene, 1,3,5-trimethyl** & 0.12 & 0.03 & 3.41 \\ Dichlorodifluoromethane & 0.03 & 0.01 & 1.80 \\
**Dodecane** & 0.13 & 0.11 & 1.27 \\
**N-Morpholinomethyl-isopropyl-sulfide** & 0.32 & 0.23 & 1.37 \\
**Nonanal** & 0.30 & 0.11 & 2.79 \\
**Undecane, 4,7-dimethyl** & 0.17 & 0.11 & 1.54 \\ \hline \hline \end{tabular}
\end{table} 
Table 2: Volatile compounds that showed \(\geq 100\%\) enrichment in melanoma compared to the healthy skin sample with the % Total Ion Count, (%TIC) and their ratios in Melanoma vs Skin and M/S ratios. In another study, [PERSON] and his co-workers conducted an untargeted approach to detect and compare volatile metabolomic signatures of melanoma sample (M) and keratinocyte carcinoma (KC) samples, using healthy adjacent skin as a control from the same patient to be collected, and analyzed on the same day. Non-melanoma cases were confirmed histologically after testing excisional biopsy samples and assured the absence of residual melanoma.