GSE168013
High-plex spatial RNA profiling reveals cell type-specific biomarker expression during melanoma development
Early diagnosis of melanoma is critical for improved survival. However, biomarkers of early melanoma evolution and their origin within the tumor and its microenvironment, including the keratinocytes, are poorly defined. To address this, we used spatial transcript profiling that maintains the morphological tumor context to measure expression of >1,000 RNAs in situ in patient-derived formalin-fixed, paraffin-embedded tissue sections in primary melanoma and melanocytic nevi. We profiled 134 200µm-diameter regions of interest enriched in melanocytes, neighboring keratinocytes or immune cells. This approach captured distinct expression patterns across cell types and tumor types during melanoma development. Unexpectedly, we discovered that S100A8 is expressed by keratinocytes within the tumor microenvironment during melanoma growth. Immunohistochemistry of 252 tumors showed prominent keratinocyte-derived S100A8 expression in melanoma but not in benign tumors and confirmed the same pattern for S100A8's binding partner S100A9, suggesting that injury to the epidermis may be an early and easily detectable indicator of melanoma development Together, our results establish a framework for high-plex, spatial and cell type-specific resolution of gene expression in archival tissue applicable to the development of biomarkers and characterization of tumor-microenvironment interactions in tumor evolution. In this dataset, we capture the GeoMx DSP RNA profiling data associated with this study. The files here represent patients with melanocytic tumors (n = 16) which were profiled with the NanoString GeoMx pilot panel (n=4 patients, n=108 gene targets) or CTA developmental panel v1.0 (n=12 patients, n=1,412 gene targets). These panels were read out using Illumina sequencing according to manufacturer protocols. For access to high resolution (single channel, composite, or ROI) images please contact mkriner@nanostring.com. Overall design: This dataset contains expression data from patient FFPE samples collected during skin biopsy. Up to 16 ROIs were collected from each patient sample. H&E-stained serial sections were used to guide ROI selection by an experienced dermatopathologist.