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High-Plex Spatial RNA Profiling Reveals Cell Type‒Specific Biomarker Expression during Melanoma Development.
Maija Kiuru1, Michelle A Kriner2, Samantha Wong3
1Department of Dermatology, School of Medicine, University of California Davis, Sacramento, California, USA; Department of Pathology and Laboratory Medicine, School of Medicine, University of California Davis, Sacramento, California, USA.
The Journal of Investigative Dermatology
|October 26, 2021
Summary
Early melanoma detection improves survival. Keratinocyte-derived S100A8 and S100A9 in the tumor microenvironment indicate epidermal injury, serving as potential early melanoma biomarkers.
Area of Science:
- Oncology
- Dermatology
- Molecular Biology
- Biomarker Discovery
Background:
- Early diagnosis of melanoma is crucial for patient survival.
- Biomarkers for early melanoma evolution and their cellular origins, particularly in keratinocytes, remain poorly understood.
- The tumor microenvironment's role in melanoma development requires further investigation.
Purpose of the Study:
- To identify biomarkers associated with early melanoma development.
- To investigate the origin of these biomarkers within the tumor and its microenvironment.
- To establish a spatial, cell-type-specific gene expression analysis framework for archival tissues.
Main Methods:
- Spatial transcript profiling of patient-derived formalin-fixed, paraffin-embedded primary melanoma and melanocytic nevi.
- In situ measurement of over 1,000 RNA transcripts within defined regions of interest (melanocytes, keratinocytes, immune cells).
- Immunohistochemistry validation of key protein markers (S100A8, S100A9) in a larger cohort of tumors.
Main Results:
- Distinct gene expression patterns were observed across different cell types and tumor types during melanoma progression.
- Keratinocytes within the tumor microenvironment were found to express S100A8 during melanoma growth.
- Prominent keratinocyte-derived S100A8 and S100A9 expression was detected in melanoma but not in benign tumors.
Conclusions:
- Keratinocyte-derived S100A8 and S100A9 suggest epidermal injury as an early indicator of melanoma development.
- These findings highlight the potential of S100A8 and S100A9 as readily detectable biomarkers for early melanoma.
- The study provides a robust framework for spatial gene expression analysis in archival tissues for biomarker development and tumor microenvironment characterization.
