Abstract A006: Shared gene expression and immune pathway changes associated with progression from nevi to melanoma

Abstract

Abstract There is a need to identify biomarkers of melanoma progression to assist the development of chemoprevention strategies to lower melanoma incidence. In this study, we assessed the feasibility of creating a molecular signature for melanomagenesis using three publicly available RNA sequencing and microarray expression datasets. We performed differential expression and regularized regression analyses across nevi and melanoma samples to identify consistent genes associated with melanomagenesis. The regularized regression models demonstrated that a small number of genes could successfully distinguish between nevi and melanoma, providing evidence for the feasibility of creating a molecular signature. Differential expression analysis identified consistent upregulation of C1QB, CXCL9, CXCL10, DFNA5 (GSDME), FCGR1B, and PRAME in melanoma and consistent downregulation of SCGB1D2 in melanoma compared to nevi. Additionally, each of these genes demonstrated a linear association with the progression from benign nevi to dysplastic nevi, to radial growth phase melanoma to vertical growth phase melanoma, providing additional evidence for their role in melanomagenesis. Subsequent pathway analysis demonstrated significant enrichment of immune-related pathways among the differentially expressed genes. Overall, this study 1) demonstrates the feasibility of creating a gene signature for melanomagenesis and 2) highlights genes and pathways of interest for melanoma progression. We are in the process of generating a new dataset with benign nevi, dysplastic nevi, and melanoma with which to build and validate a molecular signature of melanoma. Citation Format: Elizabeth S. Borden, Anngela C. Adams, Kenneth H. Buetow, Melissa A. Wilson, Julie E. Bauman, Clara Curiel-Lewandrowski, H.-H. Sherry Chow, Bonnie J. LaFleur, Karen Taraszka Hastings. Shared gene expression and immune pathway changes associated with progression from nevi to melanoma [abstract]. In: Proceedings of the Second Biennial NCI Meeting: Translational Advances in Cancer Prevention Agent Development (TACPAD); 2022 Sep 7-9. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_2): Abstract nr A006.