# Skin Cancer Metabolic Profile Assessed by Different Analytical Platforms
## 3 Skin Metabolites
### The Emerging Role of Microbiota and Adipocyte-Derived Lipids  
As previously mentioned, there is growing evidence that microbiota may play a role in triggering the incidence of skin cancer. However, microbiota can also affect the treatment response for patients with melanoma [28]. A positive clinical response to treatment in melanoma patients has been associated with specific commensal gut bacteria [29]. Treatment with anti-programmed cell death protein 1 (PD-1) is beneficial for those with metastatic melanoma. The effectiveness of fecal microbiota transplantation (FMT) in combination with anti-PD-1 in melanoma patients was previously studied in clinical study to determine whether changing the gut microbiota may help treat anti-PD-1 resistance. So, in a portion of patients with advanced melanoma, fecal microbiota delivered colonoscopically in combination with anti-PD-1 successfully colonized the responders' gut and changed the tumor microenvironment, overcoming their initial resistance to anti-PD-1. Additionally, those who responded exhibited higher levels of CD8+ T cell activation, which can fight off cancers caused by altered cells, higher levels of taxa, previously linked to anti-PD-1 responses, and lower levels of myeloid cells, which express interleukin-8, necessary for the survival and proliferation of cancer cells [28].  
Immun checkpoint inhibitors (ICIs) have a significant impact on the majority of melanoma patients; nevertheless, those who do not respond to ICIs have fewer options. The effects of human gut microbiota and metabolites on ICI responses in metastatic melanoma patients were examined in a previous study using unbiased shotgun metabolomics, and it was found that ICI responders had high levels of anacardic acid. The stimulation of neutrophils and macrophages by anacardic acids boosts T-cell recruitment to tumor metastases and, thus, increases the ICI. Anacardic acid levels, which have been discovered to have anticancer characteristics, are really influenced by gut flora [30].  
On the other hand, adipocyte-derived lipids can influence the diagnosis of melanoma. Through metabolic and lipidomic analysis, researchers studied therapeutic targets for the development of novel antimetastatic medicines, as well as potential biomarkers to predict the metastatic potential of melanoma. Changes in the metabolite and lipid profiles of human melanocytes and melanoma cell lines were found to be associated with cancer metastasis, and metabolomic analysis identified aminomalonic acid as a novel potential biomarker. Furthermore, lipid research revealed a steady increase in phosphatidylinositol (PI) species with saturated and monounsaturated fatty acyl chains with increased melanoma cell metastatic potential, defining these lipids as prospective biomarkers [31].  
Despite the usefulness of Adipocytes in the diagnosis of melanoma, it was found in a previous study that they promote the growth and invasion of nearby melanoma cells. Additionally, adipocytes directly transfer lipids to melanoma cells, which modifies the metabolism of tumor cells. The fatty acid transport protein (FATP) lipid transporters that are expressed on the surface of tumor cells convey adipocyte-derived lipids to melanoma cells. Melanomas significantly overexpress FATP1/SLC27A1, one of the six members of the FATP/SLC27A family, and this Melanocyte-specific FATP1 expression works in conjunction with BRAFV600E in transgenic zebrafish to hasten the development of melanoma, an effect also observed in mouse xenograft studies [32].