Clinical and Molecular Correlates of NLRC5 Expression in Patients With Melanoma

NLRC5 is an important regulator in antigen presentation and inflammation, and its dysregulation promotes tumor progression. In melanoma, the impact of NLRC5 expression on molecular phenotype, clinical characteristics, and tumor features is largely unknown. In the present study, public datasets from the Cancer Cell Line Encyclopedia (CCLE), Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), and cBioPortal were used to address these issues. We identify that NLRC5 is expressed in both immune cells and melanoma cells in melanoma samples and its expression is regulated by SPI1 and DNA methylation. NLRC5 expression is closely associated with Breslow thickness, Clark level, recurrence, pathologic T stage, and ulceration status in melanoma. Truncating/splice mutations rather than missense mutations in NLRC5 could compromise the expression of downstream genes. Low expression of NLRC5 is associated with poor prognosis, low activity of immune-related signatures, low infiltrating level of immune cells, and low cytotoxic score in melanoma. Additionally, NLRC5 expression correlates with immunotherapy efficacy in melanoma. In summary, these findings suggest that NLRC5 acts as a tumor suppressor in melanoma via modulating the tumor immune microenvironment. Targeting the NLRC5 related pathway might improve efficacy of immunotherapy for melanoma patients.