Characterizing dermal transcriptional change in the progression from sun-protected skin to actinic keratosis. II[

Here we used a pan-cytokeratin antibody to differentiate the epidermal from dermal compartment and assayed over 18,000 RNA probes from multiple regions of interest (ROI) comparing sun protected skin, and two regions (edge and center) from AK/sun damaged skin. This allows for a trajectory from sun protected to sun damaged within an individual. Traditionally, cancer biology focusses on change within the tumor compartment for diagnosis and staging and current genetic profiling of actinic keratosis (the precursor lesion for cutaneous squamous cell carcinoma) has focused on analysis limited to whole skin or the epidermal compartment alone. Here we use spatial transcriptomics to compare and contrast the epidermal and stromal compartments from different regions of actinic keratosis and matched sun protected skin from six individuals. Our data show that the major changes in AK at the transcriptional level are evident in the dermal compartment. Sun protected skin (n=5-6 from 6 individuals for a total of 34 ROI), the center of an AK lesion (n=3 for a total of 18 ROI) and edge of the AK lesion (n=2-3 for a total of 17 ROI) representing sun-damaged skin, from six unrelated individuals, the center of an AK lesion (n=3 for a total of 18 ROI) and edge of the AK lesion (n=2-3 for a total of 17 ROI) representing sun-damaged skin, from six unrelated individuals. Overall design: We separate out the raw data from two different experiments done approximately 6 months apart and at two different laboratories, one was run at Nanostring (UACC_dermal_transcriptional_change_from_sunProtected_to_actinic_kertosis_expirement_txt), Seattle, WA and the other at Thomas Jefferson University (UACC_dermal_transcriptional_change_from_sunProtected_to_actinic_kertosis_expirement2.txt). The initial two samples were a pilot study to ensure that pan-cytokeratin antibodies on the Nanostring DSP assay would allow for evaluation of transcriptional changes in the dermal compartment of the skin in existing samples collected at the University of Arizona. The second set of samples were run a the Core facility of Thomas Jefferson University after extramural funding (through a genomic supplement) had been obtained.