# Skin Cancer Metabolic Profile Assessed by Different Analytical Platforms
## 7 Skin Cancer Metabolomics Using Different Analytical Platforms  
### GC-MS Based Skin Cancer Metabolomics  
Among several analytical techniques used in the metabolomic analysis, GC-MS based metabolomics is the most spectral reproducible, and allows the measurement of volatile/semi-volatile thermally stable metabolites [44]. Many studies confirmed and linked the strong olfactory capability of dogs to distinguish and detect cancer from non-cancer samples to the presence of volatile molecules in the headspace over melanoma [40; 41; 42]. The analysis of volatile organic compounds (VOC) as cancer biomarkers is both challenging and promising and is considered a novel diagnostic approach to detect cancer by metabolomic analysis of breath and urine, as well as skin [45]. [PERSON] and his group expanded their efforts to achieve an early melanoma detection by identifying melanoma volatile metabolic signatures using untargeted GC-MS based metabolomic analysis. Forty-nine male melanoma patients were involved in this study, and samples were obtained from fresh melanoma tissues and nearby non-neoplastic healthy skin tissues, collected from the same patient, to be used as control. Firstly, an excisional biopsy sampling method was used to collect the samples using 2-mm punch device, one month after melanoma diagnosis was obtained, followed by the collection of volatile compounds using the Head Space Solid Phase Micro-Extraction method (HS-SPME) [46]. This method of VOC collection above cancerous tissues will probably become a non-invasive in situ collection \begin{table}
\begin{tabular}{p{113.8 pt} p{113.8 pt} p{113.8 pt} p{113.8 pt}} \hline \hline
**Sampling Method** & **Advantages** & **Disadvantages** \\ \hline Biopsy [38] & \(\bullet\) & Specimens can be collected from or beneath the epidermis (including superficial fat and dermis) & \(\bullet\) & Patient unfriendly (invasive technique) Time-consuming \\ \hline Suction-blister [38] & \(\bullet\) & Less invasive compared to skin biopsy Can be used to collect the epidermis and interstitial fluid & \(\bullet\) & Time consuming Specialized equipment required \\ \hline Tape stripping [39] & \(\bullet\) & Minimally invasive technique Collect samples from the stratum corneum & & Sample preparation often needs to be completed before metabolite analysis such as sample clean-up, extraction, and analyte preconcentration. Lack of standardized protocols \\ \hline Ultrasound [42] & \(\bullet\) & Efficient extraction & \(\bullet\) & Possible denaturation of the metabolite Many impurities \\ \hline Iontophoresis [40] & \(\bullet\) & Minimally invasive technique & \(\bullet\) & Local stimulation (partial penetration of the skin) \\ \hline Microdialysis [41] & \(\bullet\) & Minimally invasive technique Can also be used for sampling interstitial fluid in the skin by implanting thin tubular membranes & \(\bullet\) & Time consuming Limited to small molecules \\ \hline Microneedle Patches [43] & \(\bullet\) & Minimally invasive technique Helpful in collecting skin interstitial fluid & \(\bullet\) & Limited extraction efficiency \\ \hline \hline \end{tabular}
\end{table} 
Table 1: Several sample collection methods for skin metabolomic analysis. without the need of biopsies in the future, thus speeding up biomarker discovery and validation. GC-MS was used to separate and analyze volatile compounds. However, many of these compounds could not be identified due to sample complexity. In summary, this study identified 32 volatile compounds, 9 of which showed 100% enrichment in melanoma samples compared to healthy skin tissues (Table 2), and 23 were distinguished only in melanoma and not in normal tissues (Table 3). In addition to volatile compound collection and analysis, histologic analysis was performed for melanoma and healthy skin samples using hematoxylin/eosin staining.