Stratification of Cutaneous Squamous Cell Carcinomas According to Its Transcriptomic, Metabolic and Inflammatory Characteristics

Skin cancers are the most common type of cancer in human. Among them, cutaneous squamous cell carcinomas (cSCCs) represent the 2nd most frequent, with an incidence that continues to grow (+300% between 1994 and 2006) in line with the ageing of the population and sun exposure habits. cSCCs is a multi-stage carcinogenesis model: the pre-cancerous lesion is actinic keratosis (AK), which can either regress or progressively evolve into cSCC in situ and then infiltrating, and in some patients into a metastatic stage, initially lymph node and then distant, life-threatening. cSCCs are classified as low-risk or high-risk according to clinical and histological criteria associated with the risk of recurrence and metastasis. However, there is currently no tool for predicting this risk for a given cSCC, particularly according to its genetic characteristics. Indeed, the high mutation rate makes it difficult to identify specific genetic profiles. Similarly, there is no tool to predict the potential for a precancerous lesion (AK) to regress or to develop into a cSCC. The aim of this study is to characterize the molecular and metabolic features as well as immunologic landscapes of precancerous AK and cSCCs in order to uncover epithelial and immune cell subpopulations supporting tumor progression.