Discovery of Distinctive Set of Gene Expression Patterns Changes Understanding of Atypical Mole Development and Early Melanoma

LOS GATOS, Calif., June 20, 2023 /PRNewswire/ -- Researchers evaluating and comparing the gene expression profiles of common (non-malignant) moles and melanoma, the most aggressive skin cancer, have found that the transition from benign tissue to early-stage melanoma involves the reorganizing or "remodeling" of the surrounding skin structural tissue, a process that also has its own distinctive patterns of gene expression. The analysis by researchers from Orlucent, Inc. and the University of California, San Diego appears in a peer-reviewed article published in the July 2023 issue of The American Journal of Pathology.

Some common moles may exhibit abnormal features and are referred to as atypical or dysplastic nevi. But many experts believe these do not progress to melanoma, based on evidence that only 30% of melanomas are associated with common moles. However, the newly published analysis shows that dysplastic nevi are more similar to melanoma than previously believed and may contain genetic changes that can support the transition to melanoma.

"These findings demonstrate that dysplastic nevi do, in fact, have the genetic ability to transition to melanoma when supported by molecular signatures and genetic pathways related to remodeling activities of the surrounding structural tissues," Catherine Shachaf, Ph.D., the corresponding author of the study and president of Orlucent said. "These remodeling processes include the gene expression of cancer-associated fibroblasts (CAFs), collagens, extracellular matrix (ECM), and integrins. These cells and proteins assist in the development of early melanoma, as well as the immune surveillance process that plays a substantial role at this early stage."

Physicians typically spot melanoma, the most aggressive type of skin cancer, through visual examination of moles using the established ABCDE criteria, sometimes with the aid of dermoscopy. To develop into melanoma, dysplastic nevi must undergo genetic changes while also receiving various means of support from the surrounding tissue.

Shachaf points out that it is possible to identify tissue remodeling processes through gene and protein expression patterns to objectively measure their progression or regression during the various stages of melanoma development.

"The ability to measure and assess the presence of biological tissue remodeling activity adds another tool to the clinician's toolbox for assessing the development of atypical moles, one that complements their current methods of visual examination and histopathology analysis," Shachaf said. "Helping clinicians understand the biological activity occurring inside the skin can significantly transform the identification, diagnosis, and clinical management of these moles."

To conduct the analysis, the researchers reanalyzed publicly available RNA sequencing and microarray data sets with particular focus on very early stages of melanoma. They evaluated and compared gene expression profiles of four different kinds of moles or nevi—common nevi in healthy individuals, common nevi that were adjacent to melanoma, dysplastic nevi, and nevi diagnosed as melanoma.

In addition to their findings on remodeling, the researchers found that common nevi adjacent to melanoma were more similar to melanoma than to common nevi in healthy individuals. The authors also found that 53 genes significantly overlap in dysplastic nevi and melanoma, substantiating the notion that dysplastic nevi can serve as a transitional phase between common nevi and melanoma. Several of these genes, associated with the remodeling of surrounding tissue, were commonly expressed in both dysplastic nevi and in early stages of melanoma development.

Using technology that measures tissue remodeling activity, Orlucent is developing a handheld point-of-care molecular-based imaging system designed to noninvasively identify and clinically assess the development of atypical moles in adults. In the U.S., the system recently received the FDA's Breakthrough Device Designation, which is especially relevant for the estimated 2% to 53% of the adult U.S. population that have atypical moles suspicious of becoming melanoma.

The peer-reviewed article is titled, "Transcriptome Analysis Identifies Oncogenic Tissue Remodeling During Progression from Common Nevi to Early Melanoma," and can be found at https://www.sciencedirect.com/science/article/pii/S0002944023001347.

About Orlucent (www.orlucent.com)

Orlucent, Inc. is developing the Orlucent® Skin Fluorescence Imaging System, an in vivo molecular imaging system. Between 2% and 53% of the U.S. population have atypical/dysplastic moles suspicious of becoming melanoma and the in-office Orlucent system will provide the physician with information on the mole's biological activity as part of their clinical assessment. The first-of-a-kind product uses a topically-applied small peptide fluorescent dye and handheld imager to non-invasively detect a biomarker of early tissue changes and to report the level of potential concern for transition to melanoma.

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SOURCE Orlucent, Inc.