Abstract

Aim Cytoplasmic polyadenylation element-binding protein 3 (CPEB3) has been acknowledged as a tumor-suppressive gene in several cancers; however, there are few reports on the clinical significance of CPEB3 in melanoma. The aim of this study was to investigate the role of CPEB3 in predicting the prognosis of melanoma patients. Methods The association of CPEB3 expression and clinical pathologic features was performed using The Cancer Genome Atlas (TCGA) data set. The role of CPEB3 expression in prognosis was also analyzed. In addition, CPEB3 expression-related pathways were enriched by gene set enrichment analysis (GSEA). Association analysis of CPEB3 gene expression and immune infiltration was performed by ssGSEA. Results The mRNA was significantly less in melanoma than in normal tissues (p < 0.001). The decrease in CPEB3 expression in melanoma was significantly correlated with T staging (p < 0.001), clinical staging (p = 0.029), melanoma Clark level (p = 0.014), and melanoma ulceration (p = 0.003), while it was marginally significant in N staging (p = 0.089). Melanoma with low CPEB3 expression was associated with worse OS (overall survival), progression-free survival (PFS), and disease-specific survival (DSS) than in that with high expression. In the univariate analysis, expression of CPEB3, melanoma ulceration, Clark level of melanoma, age, clinical stage, T stage, and N stage were correlated with OS (p < 0.05). Further analysis by multivariate Cox regression showed that N stage (p = 0.029), melanoma ulceration (p = 0.004), and CPEB3 expression (p < 0.001) were independent prognostic factors of OS in melanoma. Moreover, GSEA showed that several pathways were enriched in CPEB3, such as PD1 signaling, CTLA4 pathway, CTCF pathway, CHEMOKIN signaling, VEGF signaling, and JAK-STAT pathway. CPEB3 was significantly correlated with the infiltration level of B cells (p < 0.001), T cells (p < 0.001), T helper cells (p < 0.001), and central memory T (Tcm) cells (p < 0.001). Conclusion CPEB3 may be a potential prognostic marker in melanoma with poor survival. Moreover, PD1 signaling, CTLA4 pathway, CTCF pathway, CHEMOKIN signaling, VEGF signaling, and JAK-STAT pathway may be the key pathway regulated by CPEB3. Moreover, the expression of CPEB3 in melanoma is related to the level of immune infiltration.

Highlights

  • Melanoma is a cancer that originates in the melanocytes [1]

  • The mortality of melanoma has remained stable [5], which reinforces the importance of discovering new biomarkers to perform early prediction, diagnosis, prognosis, and therapy of melanoma

  • Lin et al reported that epigenetic silencing of Cytoplasmic polyadenylation element-binding protein 3 (CPEB3) can promote the proliferation of colorectal cancer (CRC) cells and inhibit the apoptosis of CRC cells, providing a new prognostic marker for CRC patients [10]

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Summary

Introduction

Melanoma is a cancer that originates in the melanocytes [1]. Among reported cancers, melanoma is the fifth most common in men and sixth most common in women [2]. It is estimated that by 2020, 100,350 new cases of melanoma will be diagnosed in BioMed Research International the US and 6,850 people will die from the disease [4]. The cost of diagnosis and treatment of melanoma is 10 times greater than that of other skin cancer [1]. Ultraviolet (UV) exposure and genetic predisposition remain the most important risk factors for the development of melanoma [1]. Diagnosis and treatment of melanoma lead to better outcomes, and the introduction of immunotherapy and targeted therapy has provided much needed therapies for advanced disease [2]. The percentage of potentially fatal melanoma tumors has remained stable, with very little change in mortality over time [5], which reinforces the importance of continued research on the molecular mechanism of melanoma development and potential diagnostic and therapeutic targets

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