A Melanoma-Specific Gene Network Analysis Identifies MZB1 as a Potential Tumor Promoter

Resistance to targeted therapy and immunotherapy is a major barrier to successful metastatic melanoma treatment. Interestingly, many genes can govern melanoma cell proliferation and progression mechanisms while simultaneously modulating the tumor microenvironment and tumor immunity. Using human melanoma sample datasets, we performed a melanoma-specific immunoregulatory gene network analysis and identified 5 differentially expressed immune-related genes that significantly affect the survival of patients with melanoma. Through immunohistochemistry analysis of human melanoma tissue microarray, we found that MZB1 was the strongest candidate associated with melanoma progression. We further found that MZB1 knockdown in human melanoma cell lines decreased proliferation in vitro and xenograft tumor growth in vivo. To determine immune-related mechanisms of MZB1, we coupled NanoString nCounter Profiling of MZB1-knockdown melanoma cells with Ingenuity Pathway Analysis. We identified that MZB1 knockdown modulated the expression of numerous gene classes, including cytokines and class II HLA members. Overall, our study shows that MZB1 is a potential tumor promoter in melanoma and could be explored as a target for melanoma management.