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Keratins (KRTs), the intermediate filament-forming proteins of epithelial cells, are extensively used as diagnostic biomarkers in cancers and associated with tumorigenesis and metastasis in multiple cancers. However, the diverse expression patterns and prognostic values of KRTs in melanoma have yet to be elucidated. In the current study, we examined the transcriptional and clinical data of KRTs in patients with melanoma from GEO, TCGA, ONCOMINE, GEPIA, cBioPortal, TIMER and TISIDB databases. We found that the mRNA levels of KRT1/2/5/6/8/10/14/15/16/17 were significantly differential expressed between primary melanoma and metastatic melanoma. The expression levels of KRT1/2/5/6/10/14/15/16/17 were correlated with advanced tumor stage. Survival analysis revealed that the high transcription levels of KRT1/5/6/14/15/16/17 were associated with low overall survival in melanoma patients. GSEA analysis indicated that the most involved hallmarks pathways were P53 pathway, KRAS signaling, estrogen response early and estrogen response late. Furthermore, we found some correlations among the expression of KRTs and the infiltration of immune cells. Our study may provide novel insights for the selection of prognostic biomarkers for melanoma.

Skin cutaneous melanoma (SKCM) is one of the most deadly malignancies. Although immunotherapies showed the potential to improve the prognosis for metastatic melanoma patients, only a small group of patients can benefit from it. Therefore, it is urgent to investigate the tumor microenvironment in melanoma as well as to identify efficient biomarkers in the diagnosis and treatments of SKCM patients. A comprehensive analysis was performed based on metastatic melanoma samples from the Cancer Genome Atlas (TCGA) database and ESTIMATE algorithm, including gene expression, immune and stromal scores, prognostic immune-related genes, infiltrating immune cells analysis and immune subtype identification. Then, the differentially expressed genes (DEGs) were obtained based on the immune and stromal scores, and a list of prognostic immune-related genes was identified. Functional analysis and the protein-protein interaction network revealed that these genes enriched in multiple immune-related biological processes. Furthermore, prognostic genes were verified in the Gene Expression Omnibus (GEO) databases and used to predict immune infiltrating cells component. Our study revealed seven immune subtypes with different risk values and identified T cells as the most abundant cells in the immune microenvironment and closely associated with prognostic outcomes. In conclusion, the present study thoroughly analyzed the tumor microenvironment and identified prognostic immune-related biomarkers for metastatic melanoma., (© 2020 The Author(s).)

Background: 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., Methods: 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., Results: 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., Conclusions: 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., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Cutaneous melanoma (CM) is known as an aggressive malignant cancer; some of which are directly derived from melanocytic nevi, which have been attracting growing attention from the last decades. This study focused on comprehensive identification, validation, and functional annotations of prognostic differentially expressed genes (DEGs) between melanocytic nevus and malignant melanoma in genome-wide profiles. DEGs were obtained using three chip datasets from GEO database to identify after standardization annotation. A total of 73 DEGs were identified as possible candidate prognostic biomarkers between melanocytic nevus and malignant melanoma. In addition, survival curves indicated that six hub genes, including FABP5 , IVL , KRT6A , KRT15 , KRT16 , and TIMP2 , were significant prognostic signatures for CM and of significant value to predict transformation from nevi to melanoma. Furthermore, immunohistochemistry staining was performed to validate differential expression levels and prognostic implications of six hub genes between CM tissue and nevus tissues from the First Affiliated Hospital of Soochow University cohort. It suggested that significantly elevated FABP5 , IVL , KRT6A , KRT15 , KRT16 , and TIMP2 proteins expressed in the CM than in the nevus tissues. Functional enrichment and significant pathways of the six significant hub genes indicated that the mostly involved hallmarks include the P53 pathway, K-ras signaling, estrogen response late, and estrogen response early. In summary, this study identified significant DEGs participating in the process of malignant transformation from nevus to melanoma tissues based on comprehensive genomic profiles. Transcription profiles of FABP5 , IVL , KRT6A , KRT15 , KRT16 , and TIMP2 provided clues of prognostic implications, which might help us evaluate malignant potential of nevus and underlying carcinogenesis progress from melanocytic nevus to melanoma., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Wei Han et al.)

Uveal melanoma (UVM) is an adult intraocular malignancy which is the most frequent and has a high tendency for metastasis. This study aims to develop significant differential gene subnetwork between primary and metastatic UVM to identify potential prognostic biomarkers. Differentially expressed genes (DEGs) among three chip datasets were downloaded from Gene Expression Omnibus and identified according to standardization annotation information. Genetic enrichment analyses were utilized to describe biologic functions. The protein-protein interaction network of DEGs was developed and the module analysis was constructed by STRING and Cytoscape. Kaplan-Meier method of the integrated expression score was applied to analyze survival outcomes. Functional annotation was assessed to perform GO and Kyoto Encyclopedia of Genes and Genomes enrichment analysis. In addition, ClueGO and gene set enrichment analysis were analyzed to detect underlying significant genes and involved signaling pathways. A total of 103 DEGs with function enrichment were recognized and might be considered as candidate prognostic biomarkers between primary and metastatic UVM. Furthermore, Kaplan-Meier method suggested that SCD5, SPTBN1, FABP5, SQLE, PTPLA (HACD1), and CDC25B were independent prognostic factors in UVM. Functional annotations indicated that the most involved significant pathways including interferon-gamma response, IL-6 JAK STAT3 signaling, TNFA signaling via NFKB and inflammatory response. Significant DEGs between primary and metastatic UVM tissue were identified and might have involved in the metastasis of UVM. SCD5, SPTBN1, FABP5, SQLE, PTPLA (HACD1), and CDC25B transcription levels were of high prognostic value, which might assist us to understand the underlying carcinogenesis or advancement of UVM better., (© 2019 Wiley Periodicals, Inc.)

Background: Minichromosome maintenance (MCM) is known for participating in cell cycle progression, as well as DNA replication. While the diverse expression patterns and prognostic values of MCM s in melanoma still remained unclear. Methods: In the present study, the transcriptional and clinical profiles of MCM s were explored in patients with melanoma from multiple databases, including GEO, TCGA, ONCOMINE, GEPIA, UALCAN, cBioPortal, and TIMER databases. Results: We found that the elevated expressions of MCM2–6 and MCM10 were significantly expressed in melanoma compared to normal skin. High mRNA levels of MCM4 , MCM5 , and MCM10 were closely related to worse prognosis in patients with melanoma. GSEA showed hallmark pathways were most involved in mTORC1 signaling, G2M checkpoint, E2F targets, and mitotic spindle. Furthermore, we found potential correlations between the MCM expression and the immune cell infiltration, including B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells. Conclusion: Upregulated MCM gene expression in melanoma probably played a crucial part in the development and progression of melanoma. The upregulated MCM4/5/10 expressions could be used as potential prognostic markers to improve the poor outcome and prognostic accuracy in patients with melanoma. Our study might shed light on the selection of prognostic biomarkers as well as the underlying molecular pathogenesis of melanoma. [ABSTRACT FROM AUTHOR]