# Skin Cancer Metabolic Profile Assessed by Different Analytical Platforms
## 7 Skin Cancer Metabolomics Using Different Analytical Platforms
### LC-MS Based Skin Cancer Metabolomics
which corresponds to the mass range of most predicted metabolites, metabolic profiling was performed using UPLC on frozen human tissues, which revealed significantly different levels of metabolites in the melanoma tissue, when primary or metastatic melanoma was compared to EM (75% and 68%), respectively. In contrast, there were no significant variations between the abundances of the metabolites in primary and metastatic melanoma. Pathway-based analysis revealed three significantly important pathways between primary melanoma and EM; ascorbate and Aldarate metabolism, propanoate metabolism, and tryptophan metabolism, as well as three significant pathways between metastatic melanoma and EM; ascorbate and Aldarate metabolism, pyrimidine metabolism, and histidine metabolism. Most individual metabolite abundances found within these pathways were directionally consistent, such that the majority of compounds found to be more or less abundant in primary melanoma compared to EM were also more or less abundant in metastatic melanoma compared to EM. The metabolites in the Aldarate and ascorbate metabolic pathway set the primary and metastatic melanoma's metabolites apart from those of EM. The metabolic pathways for tryptophan and propanoate separated initial melanoma from EM but not metastatic melanoma from EM, indicating that these pathways may be crucial for the carcinogenesis of melanoma. The metabolic pathways for pyrimidine and histidine, however, were unable to differentiate primary melanoma from EM. This data suggests that rather than its initiation, these pathways may be crucial to the progression of melanoma, and the proteins or metabolites in these pathways may function as possible treatment targets to prevent metastasis [52]. In another study, the effectiveness of the monoclonal anti-programmed-death-1 (PD-1) antibody drug, Nivolumab [53], was examined in research including 82 patients with metastatic renal cell carcinoma (RCC) and 79 patients with advanced melanoma [54]. The authors discussed the safety and effectiveness of nivolumab in several malignancies to date, including advanced melanoma, renal cell carcinoma (RCC), and non-small cell lung cancer (NSCLC). Tumor cells were hypothesized to manipulate signals that decrease T-cell responses, in the evasion of the immune system. Both PD-1 on the T cell and its ligand PD ligand1 (PD-L1) on the tumor cell interact in a significant way to cause this event. Nivolumab and other PD-1 pathway inhibitors are consequently able to reverse T-cell suppression and ultimately trigger antitumor responses [53]. On pre- and post-treatment blood samples from 79 patients with advanced melanoma and 82 patients with metastatic RCC receiving nivolumab, liquid chromatography-mass spectrometry was carried out. More than 100 identified metabolites were accurately assessed at baseline (before nivolumab was started), and then at different time points (4, 6, and 9 weeks), following treatment commencement, and were related to the greatest overall response as well as progression-free survival (PFS). The findings showed that the change in kynure levels in melanoma patients was strongly associated with the response to nivolumab. Additionally, worse progression-free survival (PFS) and lack of response to nivolumab were related with greater baseline levels of adenosine in RCC patients. Briefly, a correlation between the change in kynure levels and response in melanoma patients was observed. Additionally, worse PFS and lack of response to nivolumab are linked to greater baseline levels of adenosine in RCC patients. However, it was implied that serum metabolites could have a potential role as indicators of PD1 inhibition [54].