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• EAF2 plays a key role in human malignancies. • EAF2 expression was closely associated with the immune-infiltrating levels of immune cells. • EAF2 has a strong positive correlation with CD19, implying they may be functional partners in the immune response of SKCM. • EAF2 could be a promising and potential biomarkers for the diagnosis and immunotherapy in patients with melanoma. Skin cutaneous melanoma (SKCM) accounts for over 75% of skin cancer-related deaths each year. EAF2, as a member of EAF family, has been found in several cancers, however, the role of EAF2 in SKCM is rarely studied. In this study, we utilized multiple bioinformatics tools to systematically analyze the expression of EAF family and investigate the prognostic value of EAF2 in melanoma. We found both transcriptional and proteomics expression expressions of EAF2 were elevated in SKCM. Survival analysis and ROC curves showed significant diagnostic and prognostic ability of EAF2. Importantly, EAF2 expression was closely associated with the immune-infiltrating levels of B cells, CD4+ T, CD8+ T, neutrophils, macrophages and dendritic cells. Co-expression analysis showed EAF2 has a strong positive correlation with CD19, implying they may be functional partners in the immune response of SKCM. In summary, our study is the first to reveal that increased expression of EAF2 is significantly correlated with tumor progression and better prognosis in SKCM patients. The role of EAF2 in SKCM demonstrated that it might be a potential and promising biomarker for the diagnosis and prediction of prognosis in patients with SKCM. [ABSTRACT FROM AUTHOR]

Background: Skin cutaneous melanoma (SKCM) is one of the most malignant and aggressive cancers, causing about 72% of deaths in skin carcinoma. Although extensive study has explored the mechanism of recurrence and metastasis, the tumorigenesis of cutaneous melanoma remains unclear. Exploring the tumorigenesis mechanism may help identify prognostic biomarkers that could serve to guide cancer therapy. Method: Integrative bioinformatics analyses, including GEO database, TCGA database, DAVID, STRING, Metascape, GEPIA, cBioPortal, TRRUST, TIMER, TISIDB and DGIdb, were performed to unveil the hub genes participating in tumor progression and cancer-associated immunology of SKCM. Furthermore, immunohistochemistry (IHC) staining was performed to validate differential expression levels of hub genes between SKCM tissue and normal tissues from the First Affiliated Hospital of Soochow University cohort. Results: A total of 308 differentially expressed genes (DEGs) and 12 hub genes were found significantly differentially expressed between SKCM and normal skin tissues. Functional annotation indicated that inflammatory response, immune response was closely associated with SKCM tumorigenesis. KEGG pathways in hub genes include IL-10 signaling and chemokine receptors bind chemokine signaling. Five chemokines members (CXCL9, CXCL10, CXCL13, CCL4, CCL5) were associated with better overall survival and pathological stages. IHC results suggested that significantly elevated CXCL9, CXCL10, CXCL13, CCL4 and CCL5 proteins expressed in the SKCM than in the normal tissues. Moreover, our findings suggested that IRF7, RELA, NFKB1, IRF3 and IRF1 are key transcription factors for CCL4, CCL5, CXCL10. In addition, the expressions of CXCL9, CXCL10, CXCL13, CCL4 and CCL5 were positively correlated with infiltration of six immune cells (B cell, CD8+T cells, CD4+T cells, macrophages, neutrophils, dendritic cells) and 28 types of TILs. Among them, high levels of B cells, CD8+T cells, neutrophils and dendritic cells were significantly related to longer SKCM survival time. Conclusion: In summary, this study mainly identified five chemokine members (CXCL9, CXCL10, CXCL13, CCL4, CCL5) associated with SKCM tumorigenesis, progression, prognosis and immune infiltrations, which might help us evaluate several immune-related targets for cutaneous melanoma therapy. [ABSTRACT FROM AUTHOR]