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CPEB3 低表达预示黑色素瘤患者预后不良:基于 TCGA 数据的研究。

Decreased Expression of CPEB3 Predicts a Poor Prognosis in Patients with Melanoma: A Study Based on TCGA Data.

机构信息

Department of Dermatology, Cosmetology and Venereology, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong 518101, China.

The Third School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong 510515, China.

出版信息

Biomed Res Int. 2021 Jan 11;2021:8197936. doi: 10.1155/2021/8197936. eCollection 2021.

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 ( < 0.001). The decrease in CPEB3 expression in melanoma was significantly correlated with T staging ( < 0.001), clinical staging ( = 0.029), melanoma Clark level ( = 0.014), and melanoma ulceration ( = 0.003), while it was marginally significant in N staging ( = 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 ( < 0.05). Further analysis by multivariate Cox regression showed that N stage ( = 0.029), melanoma ulceration ( = 0.004), and CPEB3 expression ( < 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 ( < 0.001), T cells ( < 0.001), T helper cells ( < 0.001), and central memory T (Tcm) cells ( < 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.

摘要

目的

细胞质多聚腺苷酸化元件结合蛋白 3(CPEB3)已被确认为几种癌症中的肿瘤抑制基因;然而,关于 CPEB3 在黑色素瘤中的临床意义的报道很少。本研究旨在探讨 CPEB3 在预测黑色素瘤患者预后中的作用。

方法

使用癌症基因组图谱(TCGA)数据集分析 CPEB3 表达与临床病理特征的关系。还分析了 CPEB3 表达对预后的作用。此外,通过基因集富集分析(GSEA)富集 CPEB3 表达相关途径。通过 ssGSEA 进行 CPEB3 基因表达与免疫浸润的关联分析。

结果

黑色素瘤中的 mRNA 明显低于正常组织(<0.001)。黑色素瘤中 CPEB3 表达的降低与 T 分期(<0.001)、临床分期(=0.029)、黑色素瘤 Clark 分级(=0.014)和黑色素瘤溃疡(=0.003)显著相关,而与 N 分期(=0.089)则呈边缘显著相关。低 CPEB3 表达的黑色素瘤与高表达的黑色素瘤相比,总生存期(OS)、无进展生存期(PFS)和疾病特异性生存期(DSS)较差。单因素分析显示,CPEB3 表达、黑色素瘤溃疡、黑色素瘤 Clark 分级、年龄、临床分期、T 分期和 N 分期与 OS 相关(<0.05)。多因素 Cox 回归分析进一步表明,N 分期(=0.029)、黑色素瘤溃疡(=0.004)和 CPEB3 表达(<0.001)是黑色素瘤 OS 的独立预后因素。此外,GSEA 显示 CPEB3 富集了几个途径,如 PD1 信号通路、CTLA4 通路、CTCF 通路、趋化因子信号通路、VEGF 信号通路和 JAK-STAT 通路。CPEB3 与 B 细胞(<0.001)、T 细胞(<0.001)、T 辅助细胞(<0.001)和中央记忆 T(Tcm)细胞(<0.001)的浸润水平显著相关。

结论

CPEB3 可能是一种具有不良生存预后的黑色素瘤潜在预后标志物。此外,PD1 信号通路、CTLA4 通路、CTCF 通路、趋化因子信号通路、VEGF 信号通路和 JAK-STAT 通路可能是 CPEB3 调节的关键通路。此外,黑色素瘤中 CPEB3 的表达与免疫浸润水平有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfb9/7815395/11bd2d8a088e/BMRI2021-8197936.001.jpg

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