# Skin Cancer Metabolic Profile Assessed by Different Analytical Platforms
## 1 Introduction  
Cancer is a public health issue that is considered the second leading cause of death worldwide. It is expected that cancer will replace cardiovascular disease (CVD) as the first cause of death worldwide, in the coming years. However, with the continuous and simultaneous advances in cancer diagnosis and treatment, survivor numbers keep increasingsignificantly as well. According to the GLOBOCAN estimates, new cancer cases and deaths continued to rise between 2018 and 2020, from 18.1 million [1] to 19.3 million new cases (1.2 million accounting for keratinocyte carcinoma) [2] and 9.6 million deaths [1] to almost 10.0 million deaths from cancer, (0.1 million accounting for keratinocyte carcinoma) [2].  
Skin is the largest organ covering the entire human body [3]. It is composed of multiple cell types, including melanocyte cells [4]. Skin cancers are the most common types of cancers with an increasing prevalence globally [5]. A previous study provides strong distinctive evidence which strengthens the hypothesis that climate factors, such as ambient air pollution, global warming, and ozone depletion can lead to an increased rate of skin malignancies globally. It is expected that these factors will continue affecting skin cancer incidence negatively in the coming decades [6]. Early diagnosis and appropriate treatment plans are highly important to achieve survival rates that may reach 99%, depending on the type of skin cancer [4]. Skin cancer is mainly triggered by exposure to ultraviolet rays [3]. However, there is rising evidence that microbiota may also contribute to skin cancer pathogenesis. Although little is known about its role in skin cancer, the recognized association between the knowledge that microbiota modifies the effect of UV-induced immunosuppression, and microbial dysbiosis and inflammation concepts has been explored [5]. Other causes of skin cancer are constant exposure to sunburns and drugs lowering immune system [4].  
Skin cancer is classified as melanoma and keratinocyte carcinoma (KC). Melanoma, or malignant melanoma (MM), is considered the riskiest and most lethal type of skin cancer [3]. However, it accounts for only 4% of skin cancer cases, and encompasses 75% of skin cancer-associated deaths because patients are unable to recognize the growth of malignant cells in the initial stages. MM includes various subtypes based on its histopathological features, somatic mutation pattern, and its anatomical distribution. In the case of MM, early diagnosis may be challenging because its morphological characteristics frequently overlap with atypical melanocytic nevi. When MM is suspected, a histopathological examination is routinely performed using a skin biopsy. Although currently considered the gold standard diagnostic for MM diagnosis, it is labor-intensive, time consuming, and can be inconclusive in borderline cases [5].  
On the other hand, KC involves all cutaneous malignant neoplasms not related to melanocytes [7]. Including cutaneous squamous cell carcinoma (CSCC), basal cell carcinoma (BCC), cutaneous adnexal tumors, and Merkel cell carcinoma (MCC). KC accounts for 95% of malignant skin cancers [8; 9]. CSCC and BCC compromise up to 99% of KCs [7] and are mainly present as localized tumors, not locally advanced or metastatic, and are usually treated with radiotherapy or curative surgery. Furthermore, MCC presents with distant metastasis and is considered one of the most aggressive and rare KCs [8].