Melanoma accounts for 80% of skin cancer deaths. The pathogenesis of melanoma is regulated by gene networks. Thus, we aimed here to identify gene networks and hub genes associated with melanoma and to further identify their underlying mechanisms. GTEx (normal skin) and TCGA (melanoma tumor) RNA-seq datasets were employed for this purpose. We conducted weighted gene co-expression network analysis (WGCNA) to identify key modules and hub genes associated with melanoma. Log-rank analysis and multivariate Cox model analysis were performed to identify prognosis genes, which were validated using two independent melanoma datasets. We also evaluated the correlation between prognostic gene and immune cell infiltration. The blue module was the most relevant for melanoma and was thus considered the key module. Intersecting genes were identified between this module and differentially expressed genes (DEGs). Finally, 72 genes were identified and verified as hub genes using the Oncomine database. Log-rank analysis and multivariate Cox model analysis identified 13 genes that were associated with the prognosis of the metastatic melanoma group, and RTP4 was validated as a prognostic gene using two independent melanoma datasets. RTP4 was not previously associated with melanoma. When we evaluated the correlation between prognostic gene and immune cell infiltration, we discovered that RTP4 was associated with immune cell infiltration. Further, RTP4 was significantly associated with genes encoding components of immune checkpoints (PDCD1, TIM-3, and LAG3). RTP4 is a novel prognosis-related hub gene in cutaneous melanoma. The novel gene RTP4 identified here will facilitate the exploration of the molecular mechanism of the pathogenesis and progression of melanoma and the discovery of potential new target for drug therapy.

中文翻译：

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RTP4是皮肤黑色素瘤中一种新型的预后相关枢纽基因


黑色素瘤占皮肤癌死亡人数的 80%。黑色素瘤的发病机制受基因网络调控。因此，我们的目的是确定与黑色素瘤相关的基因网络和中心基因，并进一步确定其潜在机制。 GTEx（正常皮肤）和 TCGA（黑色素瘤）RNA-seq 数据集用于此目的。我们进行了加权基因共表达网络分析（WGCNA）来识别与黑色素瘤相关的关键模块和中心基因。进行对数秩分析和多变量 Cox 模型分析来识别预后基因，并使用两个独立的黑色素瘤数据集进行验证。我们还评估了预后基因与免疫细胞浸润之间的相关性。蓝色模块与黑色素瘤最相关，因此被认为是关键模块。鉴定了该模块和差异表达基因（DEG）之间的交叉基因。最后，使用 Oncomine 数据库鉴定并验证了 72 个基因作为中心基因。对数秩分析和多变量 Cox 模型分析确定了 13 个与转移性黑色素瘤组预后相关的基因，并使用两个独立的黑色素瘤数据集验证了 RTP4 作为预后基因。 RTP4 以前并未与黑色素瘤相关。当我们评估预后基因与免疫细胞浸润之间的相关性时，我们发现RTP4与免疫细胞浸润相关。此外，RTP4 与编码免疫检查点成分的基因（PDCD1、TIM-3 和 LAG3）显着相关。 RTP4 是皮肤黑色素瘤中一种新型的预后相关中枢基因。 此次鉴定的新基因RTP4将有助于探索黑色素瘤发病和进展的分子机制以及发现潜在的药物治疗新靶点。