Background Melanoma is a malignant tumor of melanocytes, and the incidence has increased faster than any other cancer over the past half century. Most primary melanoma can be cured by local excision, but metastatic melanoma has a poor prognosis. Cutaneous melanoma (CM) is prone to metastasis, so the research on the mechanism of melanoma occurrence and metastasis will be beneficial to diagnose early, improve treatment, and prolong life survival. In this study, we compared the gene expression of normal skin (N), primary cutaneous melanoma (PM) and metastatic cutaneous melanoma (MM) in the Gene Expression Omnibus (GEO) database. Then we identified the key genes and molecular pathways that may be involved in the development and metastasis of cutaneous melanoma, thus to discover potential markers or therapeutic targets. Methods Three gene expression profiles (GSE7553, GSE15605 and GSE46517) were downloaded from the GEO database, which contained 225 tissue samples. R software identified the differentially expressed genes (DEGs) between pairs of N, PM and MM samples in the three sets of data. Subsequently, we analyzed the gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway of the DEGs, and constructed a protein-protein interaction (PPI) network. MCODE was used to seek the most important modules in PPI network, and then the GO function and KEGG pathway of them were analyzed. Finally, the hub genes were calculated by the cytoHubba in Cytoscape software. The Cancer Genome Atlas (TCGA) data were analyzed using UALCAN and GEPIA to validate the hub genes and analyze the prognosis of patients. Results A total of 134, 317 and 147 DEGs were identified between N, PM and MM in pair. GO functions and KEGG pathways analysis results showed that the upregulated DEGs mainly concentrated in cell division, spindle microtubule, protein kinase activity and the pathway of transcriptional misregulation in cancer. The downregulated DEGs occurred in epidermis development, extracellular exosome, structural molecule activity, metabolic pathways and p53 signaling pathway. The PPI network obtained the most important module, whose GO function and KEGG pathway were enriched in oxidoreductase activity, cell division, cell exosomes, protein binding, structural molecule activity, and metabolic pathways. 14, 18 and 18 DEGs were identified respectively as the hub genes between N, PM and MM, and TCGA data confirmed the expression differences of hub genes. In addition, the overall survival curve of hub genes showed that the differences in these genes may lead to a significant decrease in overall survival of melanoma patients. Conclusions In this study, several hub genes were found from normal skin, primary melanoma and metastatic melanoma samples. These hub genes may play an important role in the production, invasion, recurrence or death of CM, and may provide new ideas and potential targets for its diagnosis or treatment.

中文翻译：

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综合分析鉴定皮肤黑色素瘤发生转移的关键基因及信号通路

背景黑色素瘤是黑色素细胞的恶性肿瘤，近半个世纪以来发病率的增长速度超过其他任何癌症。大多数原发性黑色素瘤可通过局部切除治愈，但转移性黑色素瘤预后较差。皮肤黑色素瘤（CM）易发生转移，因此对黑色素瘤发生和转移机制的研究将有利于早期诊断、改善治疗、延长生存期。在这项研究中，我们比较了基因表达综合 (GEO) 数据库中正常皮肤 (N)、原发性皮肤黑色素瘤 (PM) 和转移性皮肤黑色素瘤 (MM) 的基因表达。然后我们确定了可能参与皮肤黑色素瘤发展和转移的关键基因和分子途径，从而发现潜在的标志物或治疗靶点。方法 从 GEO 数据库下载三个基因表达谱（GSE7553、GSE15605 和 GSE46517），其中包含 225 个组织样本。R 软件识别了三组数据中 N、PM 和 MM 样本对之间的差异表达基因 (DEG)。随后，我们分析了DEGs的基因本体（GO）功能和京都基因与基因组百科全书（KEGG）通路，并构建了蛋白质-蛋白质相互作用（PPI）网络。MCODE用于寻找PPI网络中最重要的模块，然后分析它们的GO函数和KEGG通路。最后，通过 Cytoscape 软件中的 cytoHubba 计算中心基因。使用 UALCAN 和 GEPIA 分析癌症基因组图谱 (TCGA) 数据，以验证中心基因并分析患者的预后。结果共134个，在 N、PM 和 MM 之间成对确定了 317 和 147 个 DEG。GO功能和KEGG通路分析结果表明，上调的DEGs主要集中在细胞分裂、纺锤体微管、蛋白激酶活性和癌症中的转录失调通路。下调的DEGs发生在表皮发育、细胞外外泌体、结构分子活性、代谢途径和p53信号通路中。PPI网络获得了最重要的模块，其GO功能和KEGG通路在氧化还原酶活性、细胞分裂、细胞外泌体、蛋白质结合、结构分子活性和代谢通路方面富集。14、18和18个DEGs分别被鉴定为N、PM和MM之间的枢纽基因，TCGA数据证实了枢纽基因的表达差异。此外，hub基因的总生存曲线显示，这些基因的差异可能导致黑色素瘤患者的总生存率显着下降。结论 在这项研究中，从正常皮肤、原发性黑色素瘤和转移性黑色素瘤样本中发现了几个中心基因。这些枢纽基因可能在CM的产生、侵袭、复发或死亡中发挥重要作用，并可能为其诊断或治疗提供新思路和潜在靶点。