Transcriptomic Study on Human Skin Samples: Identification of Two Subclasses of Actinic Keratoses

Actinic keratoses (AKs) are sun-damaged skin areas that affect 20% of the European adult population and more than 50% of people aged 70 years and over. There are currently no clinical or histological features allowing us to identify to which clinical class (i.e., regression or progression) an AK belongs. A transcriptomic approach seems to be a robust tool for AK characterization, but there is a need for additional studies, including more patients and elucidating the molecular signature of an AK. In this context, the present study, including the largest number of patients to date, is the first aiming at identifying biological features to objectively distinguish different AK signatures. We highlight two distinct molecular profiles: AKs featuring a molecular profile similar to squamous cell carcinomas (SCCs), which are called lesional AKs (AK_Ls), and AKs featuring a molecular profile similar to normal skin tissue, which are called non-lesional AKs (AK_NLs). The molecular profiles of both AK subclasses were studied, and 316 differentially expressed genes (DEGs) were identified between the two classes. The 103 upregulated genes in AK_L were related to the inflammatory response. Interestingly, downregulated genes were associated with keratinization. Finally, based on a connectivity map approach, our data highlight that the VEGF pathway could be a promising therapeutic target for high-risk lesions.

Automated summary

Actinic keratoses (AKs) are common sun-damaged skin areas, and there is a need for objective identification of different AK types. This study identified two molecular profiles of AKs, lesional AKs (AK_Ls) with similarity to squamous cell carcinomas and non-lesional AKs (AK_NLs) with similarity to normal skin tissue. The gene expression analysis revealed differences in inflammatory and keratinization-related genes between the two AK classes and suggested the potential of targeting the VEGF pathway for high-risk lesions.