Nischarin expression may have differing roles in male and female melanoma patients

Abstract PurposeMelanoma is the deadliest form of skin cancer. Despite the advancements in targeted and immunotherapies, metastatic melanoma patients still have poor prognosis, and there is an urgent need for novel treatment modalities. Nischarin (NISCH) is a druggable scaffolding protein shown to be a tumor suppressor in breast cancer through regulation of cancer cell survival, motility and invasion. The aim of this study was to determine NISCH expression, prognostic value, and potential role in melanoma progression.MethodsNISCH expression and regulation mechanisms were examined in publicly available data sets and on a retrospective cohort of melanoma patient tissue samples from our institution using RT-qPCR and MSP. Gene set enrichment analysis (GSEA) was used to examine the potential role of NISCH in melanoma. Tumor immune profiles were investigated using TIMER2.0 website.ResultsNISCH was expressed at both mRNA and protein level, and its expression was decreased in tumors compared to skin and nevi. Lower expression could be attributed to the presence of microdeletions and hyper-methylation of the NISCH promoter in the tumor tissue. NISCH expression in primary melanoma had favorable prognostic value for females, but high NISCH expression meant worse prognosis for males. GSEA indicated significant sex-related disparities in predicted NISCH-associated signaling pathways in melanoma. High NISCH expression in males was associated with higher content of B cells in primary tumors. ConclusionsOur data indicate that levels of NISCH expression may have an impact on melanoma progression, but that its function is different in male and female patients. Since NISCH was previously investigated only in female cancers, our findings open up a new avenue of investigation.