TMED10 expression in human cutaneous malignant melanoma

Purpose: TMED10 is involved in unconventional protein secretion and ER-Golgi trafficking. TMED10 may exert protumorigenic or oncosuppressive functions in different tumor types, but its role in human cutaneous melanoma has never been explored. Here, TMED10 expression has been investigated in human benign melanocytic tumors and cutaneous malignant melanoma (cMM). Methods: This study utilized in silico analysis on various publicly available web platforms to investigate TMED10 gene expression in normal skin and human melanoma at different Clark levels, and immunohistochemistry and digital morphometric analysis of TMED10 protein levels in 60 human samples of benign melanocytic tumors and cMMs at different Breslow T category. Results: In silico analysis revealed that TMED10 is upregulated in cMM compared to normal skin. TMED10 expression in cMM positively correlated with Clark level at diagnosis, and higher expression was associated with the BRAFV600E mutation and poorer patient survival. TMED10 co-expression with TMED2, TMED8, HSP90AA1 and HSP90B1, along with Gene Ontology enrichment analysis, supported its role in ER-Golgi trafficking and unconventional protein secretion in human melanoma. Digital morphometric analysis of immunohistochemical investigation of 60 human specimens confirmed a significant increase in TMED10 protein levels with Breslow thickness-based T category in tumor cells and tumor-associated blood vessels. At variance, TMED10 immunoreactivity in infiltrating lymphocytes was reduced in T3 and T4 cMM. Conclusion: These findings point to a pro-tumorigenic function of TMED10 in human cMM and pave the way to further studies aimed at identifying its contribution to tumor progression, neovascularization, and immune escape, and its potential as a therapeutic target in cMM.