# Skin Cancer Metabolic Profile Assessed by Different Analytical Platforms
## 7 Skin Cancer Metabolomics Using Different Analytical Platforms
### GC-MS Based Skin Cancer Metabolomics
Healthy adjacent non-neoplastic skin is the optimal control because there are differences in lipids and their secondary metabolites due to cancer progression, in addition to age and topographic related differences in the lipid structure of human skin. Like the previous study, VOCs from biopsied samples were collected using a HS-SPME device with a 0.65 um Polydimethylsiloxane/Divinylbenzene (PDMS-DVB) fiber at room temperature for one hour, and analyzed using GC-MS: however, in this study, the number of recruited patients were 10. Five patients had melanoma tumors and five were recruited with benign tumors or keratinocyte carcinoma. A 2 mm punch biopsy device was used to collect two tissue biopsies from each patient, one from a melanoma or keratinocyte carcinoma lesion and the other from healthy adjacent skin. A total of 20 tissues were analyzed, five keratinocyte carcinoma samples versus five healthy adjacent skin, and five melanomas versus five healthy adjacent skins. In addition, 10 air samples from the empty vial containing the volatile collection were analyzed. Comparison of the metabolomic signatures between three groups: skin vs. air samples, keratinocyte carcinoma vs. matching skin, and melanoma vs. matching skin is shown in (Table 4). Volatile compounds were annotated based on their retention index (RI) and spectral similarity with a library match. Palmitic and lauric acid are revealed to be significantly elevated in melanoma samples, relative to the control skin. They are listed in the Human Metabolome Database as one of the most commonly found saturated fatty acids in animals with measurable concentrations in human urine, cerebrospinal fluid, and serum [45]. Plasmalogens are essential membrane glycerophospholipids with vinyl ether linkages that present normally in the plasma membrane at an amount of no more than 1% [49]. However, more than 4% of the plasmalogens of total phospholipids indicate neoplastic transformation. The increased amount of palmitic acid in the melanoma group is highly likely related to its function as a building block for plasmalogens synthesis. Moreover, cell proliferation in cancer leads to increased lipid synthesis, which is supported by palmitic acid presence. In addition, lauric acid, a medium \begin{table}
\begin{tabular}{l} \hline \hline
**Compounds Found Only in Melanoma** \\ \hline
1,3-Cyclopentadiene, 5-(1-methylethylene)- \\
1-Eicosanol \\
1-Hexadecene \\
2-Ethoxyethyl acrylate \\
2-Isopropylamino-4-methylbenzonitrile \\ Adenosine, 5’-amino-5’-deoxy \\ Benzaldehyde, 4-methoxy \\ Bis(2-ethylhexyl) phthalate \\ Cyclohexane, ethyl \\ Decanal \\ Decane, 2-methyl \\ Decane, 4-methyl \\ Ethanol, 2-butoxy \\ Ethylene oxide \\ Formamide \\ Heptane, 2,4-dimethyl \\ Isopropyl Palmitate \\ Nonane, 1-iodo \\ Pentane, 2,3,4-trimethyl \\ Phthalic acid, isobutyl 4-octyl ester \\ Spiro [bicyclo [2.2.1] hept-5-ene-2,1’-cyclopropane] \\ Undecane \\ \hline \hline \end{tabular}
\end{table} 
Table 3: 23 Volatile compounds found only in melanoma. chain fatty acid, can be formed from increased plasma membrane lipid peroxidation and increased aldehyde dehydrogenase (ALDH) activity in many cancers, including skin cancer. It is difficult to be confident about cinnamaldehyde origin in melanoma samples because they are known to be present in cosmetics as well as skin. However, toluene was the only volatile compound found significantly decreased in melanoma samples relative to the skin controls. It is assumed that toluene is not an endogenous metabolite, but is an environmental contaminant although it was identified in a few studies as a down regulated compound in lung cancer patients (non-smokers). It is certain that none of these identified volatile compounds are secondary metabolites of the medications used by melanoma patients, because they were identified relative to the paired healthy control skin from the same patient [45].