Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, 12 Jiangwangmiao Street, Nanjing 210042, China.
Department of Dermatology, The Affiliated Qingdao Municipal Hospital of Qingdao University, Qingdao, China.
Biomed Res Int. 2020 Sep 5;2020:4985014. doi: 10.1155/2020/4985014. eCollection 2020.
Epithelial splicing regulatory protein 1 (ESRP1) has been described as an RNA-binding protein involved in cancer development. However, the expression and regulatory network of ESRP1 in cutaneous malignant melanoma (CMM) remain unclear.
From the sequencing data of 103 CMM samples in The Cancer Genome Atlas database, the expression level of ESRP1 and its correlation with the clinicopathological characteristics were analyzed using the Oncomine 4.5, Gene Expression Profiling Interactive Analysis (GEPIA), and UALCAN tools, while LinkedOmics was used to identify differential gene expression with ESRP1 and to analyze Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Gene enrichment analysis examined target networks of kinases, miRNAs, and transcription factors. Finally, TIMER was used to analyze the relationship between ESRP1 and tumor immune cell infiltration.
We found that ESRP1 was lowly expressed in CMM tissues, and a low level of ESRP1 expression correlated with better overall survival. Expression of this gene was linked to functional networks involving the condensed chromosomes, epidermal development, and translation initiation. Functional network analysis suggested that ESRP1 regulated ribosome metabolism, drug metabolism, and chemical carcinogenesis via pathways involving several cancer-related kinases, miRNAs, and transcription factors. Furthermore, our results suggested that ESRP1 played an important role in regulating tumor-associated macrophage polarization, dendritic cell infiltration, Treg cells, and T cell exhaustion.
Our study demonstrates ESRP1 expression, prognostic value, and potential regulatory networks in CMM, thereby shedding light on the clinical significance of ESRP1, and provides a novel biomarker for determining prognosis and immune infiltration in CMM.
上皮剪接调节蛋白 1（ESRP1）被描述为一种参与癌症发生的 RNA 结合蛋白。然而，其在皮肤恶性黑色素瘤（CMM）中的表达和调控网络仍不清楚。
从 The Cancer Genome Atlas 数据库中 103 个 CMM 样本的测序数据中，使用 Oncomine 4.5、Gene Expression Profiling Interactive Analysis（GEPIA）和 UALCAN 工具分析 ESRP1 的表达水平及其与临床病理特征的相关性，同时使用 LinkedOmics 识别与 ESRP1 差异表达的基因，并分析基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路。基因富集分析检查了激酶、miRNA 和转录因子的靶网络。最后，使用 TIMER 分析 ESRP1 与肿瘤免疫细胞浸润的关系。
我们发现 ESRP1 在 CMM 组织中低表达，低水平的 ESRP1 表达与更好的总生存率相关。该基因的表达与涉及浓缩染色体、表皮发育和翻译起始的功能网络相关。功能网络分析表明，ESRP1 通过涉及几种癌症相关激酶、miRNA 和转录因子的途径调节核糖体代谢、药物代谢和化学致癌作用。此外，我们的结果表明，ESRP1 在调节肿瘤相关巨噬细胞极化、树突状细胞浸润、Treg 细胞和 T 细胞耗竭方面发挥着重要作用。
本研究表明 ESRP1 在 CMM 中的表达、预后价值和潜在调控网络，从而揭示了 ESRP1 的临床意义，并为 CMM 的预后和免疫浸润提供了一种新的生物标志物。
