Spatial transcriptomics reveals a unique tumor microenvironment distinguishing the invasive region from the premalignant area in early-stage cutaneous squamous cell carcinoma.
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Presented at: Society for Investigative Dermatology 2025
Date: 2025-05-07 00:00:00
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Summary: Abstract Body: Cutaneous squamous cell carcinoma (SCC) progresses in a stepwise manner, transitioning from healthy skin to premalignant actinic keratosis (AK) and ultimately to malignant SCC. However, the gene expression changes within the tumor microenvironment throughout this progression remain underexplored. In this study, we retrospectively analyzed early-stage cutaneous SCC tissue samples containing both invasive and premalignant regions. Using the NanoString GeoMx Digital Spatial Profiler (DSP), we conducted spatial transcriptomic analyses. Regions of interest (ROIs) were selected from the invasive and premalignant areas within each tissue sample, focusing on three cellular components: tumor cells, immune cells, and fibroblasts. Gene expression patterns were compared between these regions across the 17 selected patient samples. We identified differentially expressed genes (DEGs) in each cellular component: 29 DEGs in tumor cells, 14 in immune cells, and 15 in fibroblasts. The three genes with the greatest differences in expression levels were CCDC88C, GJD3, and COMP in tumor cells; SVEP1, TSLP, and PPP2R5C in immune cells; and SPAG6, PPP1CA, and CCDC68 in fibroblasts. were associated with the development and function of cancer-associated fibroblasts. Functional enrichment analysis revealed significant alterations in various pathways, particularly within tumor and immune cells. Overall, this study highlights distinctive changes in gene expression patterns as premalignant AK evolves into invasive SCC. Jeong-An Gim<sup>1</sup>, Eun-Jung Kwak<sup>4</sup>, Chungyeul Kim<sup>2</sup>, Hyun Jyung Oh<sup>3</sup>, Jiehyun Jeon<sup>5</sup>, Aeree Kim<sup>2</sup>, Yoo Sang Baek<sup>5</sup> 1. Department of Medical Science, Soonchunhyang University, Asan, Chungcheongnam-do, Korea (the Republic of). 2. Department of Pathology, Korea University, Seoul, Korea (the Republic of). 3. Department of Biomedical Science, Korea University, Seoul, Korea (the Republic of). 4. National Dental Care Center for Person with Special Needs, Seoul National University Dental Hospital, Seoul, Korea (the Republic of). 5. Department of Dermatology, Korea University, Seoul, Korea (the Republic of). UV Biology/Injury and Non-melanoma Cancers