Pan-cancer analysis identifies ESM1 as a novel oncogene for esophageal cancer
Pan-cancer analysis identifies ESM1 as a novel oncogene for esophageal cancer
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DOI：
10.1007/s10388-020-00796-9
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发表时间：
2020-11-11
期刊：
影响因子：
2.4
通讯作者：
Guan, Fangxia
中科院分区：
文献类型：
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作者：
Cui, Yuanbo;Guo, Wenna;Guan, Fangxia
背景最近的研究强调了内皮细胞特异性分子1（ESM 1）在多种癌症类型发展中的关键作用。然而，其在人类泛癌中的异常表达和预后价值在很大程度上尚未被描述。方法和结果在这项研究中，我们使用癌症基因组图谱（TCGA）分析数据库，探讨ESM 1在33种人类癌症中的表达水平和预后意义。ESM 1在12种癌症类型中过度表达，包括BLCA，BRCA，COAD，CHOL，ESCA，HNSC，KIRC，KICH，LIHC，STAD，THCA和UCEC。ESM 1的表达与CESC、ESCA、KIRC和KIRP患者的总生存期（OS）显著相关。此外，高ESM 1水平表明ACC、ESCA、PRAD、LIHC、KIRP和UCS患者的无病生存期（DFS）较差。通过比较分析，我们发现ESM 1在食管癌（ESCA）中显著上调，并与患者OS和DFS较差相关。ESCA中ESM 1的升高通过来自癌症RNA-Seq Nexus（CRN）和基因表达综合数据集（GEO）的数据集证实。基于基因集富集分析（Gene Set Enrichment Analysis，GSEA），对ESCA中ESM 1共表达基因进行分析，发现ESM 1与细胞增殖、迁移以及Janus激酶（Janus kinase，JAK）信号通路的调控密切相关。在功能上，ESM 1的敲低显著抑制细胞增殖和迁移，并降低JAK 1的蛋白水平。总之，我们的研究结果首次表明，ESM 1作为一个癌基因的功能，并可能是一个临床生物标志物和/或治疗ESCA的目标。
Background Recent studies highlight the crucial role of endothelial cell-specific molecule 1 (ESM1) in the development of multiple cancer types. However, its aberrant expression and prognostic value in human pan-cancer have largely not been described. Methods and results In this study, we used The Cancer Genome Atlas (TCGA) analysis databases to explore the expression level and prognostic significance of ESM1 in 33 types of human cancer. ESM1 was shown to be over-expressed in 12 cancer types, including BLCA, BRCA, COAD, CHOL, ESCA, HNSC, KIRC, KICH, LIHC, STAD, THCA, and UCEC. The expression of ESM1 was significantly correlated with the overall survival (OS) of patients in CESC, ESCA, KIRC, and KIRP. In addition, high ESM1 level indicated poor disease-free survival (DFS) of patients with ACC, ESCA, PRAD, LIHC, KIRP, and UCS. Through comparative analysis, we discovered that ESM1 was dramatically up-regulated in esophageal cancer (ESCA) and associated with worse patient OS and DFS. The elevation of ESM1 in ESCA was confirmed by the datasets from Cancer RNA-Seq Nexus (CRN) and Gene Expression Omnibus (GEO). Based on Gene Set Enrichment Analysis (GSEA), we analyzed the co-expressed genes of ESM1 in ESCA, and found that ESM1 was closely implicated in cell proliferation and migration and the regulation of Janus kinase (JAK) signaling pathway. Functionally, knockdown of ESM1 significantly suppressed cell proliferation and migration, and decreased the protein level of JAK1. Conclusions Taken together, our results suggest for the first time that ESM1 functions as an oncogene and may be a clinical biomarker and/or therapeutic target in ESCA.