Abstract
ObjectiveMelanoma 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.MethodsGTEx (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.ResultsThe 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).ConclusionsRTP4 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.
Highlights
Melanoma and nonmelanoma represent the two main types of skin cancer
We discovered that RTP4 was associated with immune cell infiltration of samples of melanoma metastases, which negatively correlated with the cellular purity of melanomas and positively correlated with neutrophils (Fig. 6a)
Our aim here was to identify gene networks and hub genes associated with melanoma and to further identify the underlying mechanisms responsible for oncogenesis and tumor progression, including metastasis
Summary
Melanoma and nonmelanoma represent the two main types of skin cancer. The most common nonmelanomas are basal cell and squamous cell carcinomas. Among numerous studies aimed to identify the mechanism of melanoma, one study identified differentially expressed genes (DEGs) between metastatic and primary melanomas. These DEGs were enriched in mRNAs encoding cell adhesion and proliferation molecules. As disruption of the epigenomic landscape is recognized as a widespread feature inherent in tumor development and progression, a study of DNA methylation identified markers associated with the melanoma. These identified methylation biomarkers involved in melanoma development (e.g., HOXA9 methylation) and tumor progression (e.g., TBC1D16 methylation). Numerous genes that have somatic mutations were identified, such as BRAF and TERT [7]
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