Gene profiling technology reveals melanoma biomarkers

A new UC Davis-led study sheds light on cell type-specific biomarkers, or signs, of melanoma. The research was recently published in the Journal of Investigative Dermatology.

Melanoma, the deadliest of the common skin cancers, is curable with early diagnosis and treatment. However, diagnosing melanoma clinically and under the microscope can be complicated by what are called melanocytic nevi — otherwise known as birthmarks or moles that aren’t cancerous. Melanoma development is a multi-step process in which “melanocytes,” or cells in the skin that contain melanin, mutate and proliferate. Correct identification of melanoma at an early stage is critical to improving survival.

“Biomarkers of early melanoma evolution and their origin in the tumor and its microenvironment are a potential key to early diagnosis of melanoma,” said study corresponding author Maija Kiuru, associate professor of clinical dermatology and pathology at UC Davis Health. “To unravel the mystery, we used high-plex spatial RNA profiling to capture distinct patterns of gene expression across cell types during melanoma development.” This approach allows studying the expression of hundreds or thousands of genes without disturbing the natural architecture of the tumor.

New technology used during training

The study examined the expression of more than 1,000 genes in 134 regions of interest enriched in melanocytes, a cell in the skin and eyes that produces the pigment called melanin, as well as neighboring keratinocytes or immune cells. The tissue studied came from patient biopsies of 12 tumors ranging from benign to malignant using the NanoString GeoMx® Digital Spatial Profiler.

“We found that melanoma biomarkers are expressed by specific cell types, some by the tumor cells but others by neighboring cells in the so-called tumor microenvironment. The most striking observation was this S100A8, which is a known melanoma marker that is thought to be expressed by immune cells, is expressed by keratinocytes that make up the outermost layer of the skin, called the epidermis,” Kiuru said. “Melanoma biomarkers in the epidermis have been largely overlooked in the past.”

Keratinocytes are epidermal cells that have multiple functions, including forming a barrier against microorganisms, heat, water loss, and ultraviolet radiation. Normal keratinocytes also control melanocyte growth.

“Unexpectedly, we found this S100A8 is expressed by keratinocytes in the tumor microenvironment during melanoma growth,” said Kiuru. “We looked further S100A8 expression in 252 benign and malignant melanocytic tumors that show a pronounced keratinocyte origin S100A8 expression in melanoma but not in benign tumors. This suggests that S100A8 expression in the epidermis may be an easily detectable indicator of melanoma development.

Many molecular tests for the diagnosis and prognosis of melanoma have been gradually introduced, but markers for the early development of melanoma, especially in the tumor microenvironment, are still lacking. In addition, although the treatment of metastatic melanoma has changed dramatically since the development of immune checkpoint inhibitor therapies, biomarkers predictive of how long a patient will be cancer-free are largely unknown. Previous studies have used sophisticated methods, including single-cell RNA sequencing, but have largely focused on melanoma metastases or secondary tumor growths. This has overlooked the keratinocyte microenvironment of primary melanomas.

reference: Kiuru M, Kriner MA, Wong S, et al. High-plex spatial RNA profiling reveals cell type-specific biomarker expression during melanoma development. J. Invest. dermatology. 2022;142(5):1401-1412.e20. doi: 10.1016/j.jid.2021.06.041

This article has been republished from the following materials. Note: Material may have been edited for length and content. For additional information, please contact the cited source.

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