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EWSR1(尤因肉瘤断点区 1/EWS RNA 结合蛋白 1)的过表达预示着肝细胞癌患者的生存不良。

Overexpression of EWSR1 (Ewing sarcoma breakpoint region 1/EWS RNA binding protein 1) predicts poor survival in patients with hepatocellular carcinoma.

机构信息

Department of Pathology, The People's Hospital of Jianyang City, Jianyang, Sichuan, 641499, China.

Department of Pathology, Shandong Provincial Hospital affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China.

出版信息

Bioengineered. 2021 Dec;12(1):7941-7949. doi: 10.1080/21655979.2021.1982844.

Abstract

Hepatocellular carcinoma (HCC) is one of the most prevalent malignant neoplasms with high relapse and mortality rate. It is of great importance to identify novel and effective molecular markers to predict prognosis for the treatment of HCC. The Ewing sarcoma breakpoint region 1 (EWSR1) gene is well known to fuse with various partner genes and involved in promoting the development of multiple sarcomas, especially the Ewing sarcoma family of tumors. Nevertheless, seldom studies have focused on the role of EWSR1 in cancers of epithelial origin, let alone in HCC. In the current study, the transcriptional and clinical data of EWSR1 in HCC patients were obtained from TCGA and GEO databases, as well as 124 cases from the department of Pathology of Sichuan Jianyang People's Hospital. Kaplan-Meier and Cox regression analysis were used to assess patient prognosis. EWSR1 mRNA levels were significantly upregulated in HCC tissues than in normal liver tissues ( < 0.001). The TCGA database analysis showed upregulation of EWSR1 was associated with histological grade, pathologic T stage and death, in addition to that, the T staging, N staging, TNM staging, Ki67, AFP expression were extremely higher in the EWSR1 over-expression group in our cohort. Univariate and multivariate Cox hazard regression analysis results revealed that EWSR1 was an independent prognostic factor for OS in HCC, and bioinformatics analysis showed RNA splicing process represented the major function and pathway. In conclusion, our data showed EWSR1 could serve as a novel promising prognostic biomarker for HCC patients.: AFP, Alpha-fetoprotein; CCL14, C-C motif chemokine ligand 14; CK19, Cytokeratin 19; CI, coefficient interval; COL1A1, Collagen 1A1; DFS, Disease-free Survival; EWSR1, Ewing Sarcoma breakpoint region 1/EWS RNA binding protein 1; FLI1, Friend leukemia virus integration 1; GEO, Gene Expression Omnibus; GO, Gene Ontology; HCC, Hepatocellular carcinoma; HR, Hazard ratio; KEGG, Kyoto Encyclopedia of Genes and Genomes; mRNA, messenger Ribonucleic Acid; N, nodule; OS, Overall survival; PPI, Protein-Protein Interaction analysis; RNA, Ribonucleic Acid; SD, Standard Deviation; TCGA, The Cancer Genome Atlas; T, tumor; TNM, tumor-nodule-metastasis.

摘要

肝细胞癌(HCC)是最常见的恶性肿瘤之一,具有高复发率和死亡率。因此,识别新的有效的分子标志物对预测 HCC 的预后和治疗非常重要。Ewing 肉瘤断点区 1(EWSR1)基因已被证实与多种伙伴基因融合,并参与促进多种肉瘤的发展,尤其是尤文肉瘤家族肿瘤。然而,很少有研究关注 EWSR1 在上皮来源的癌症中的作用,更不用说在 HCC 中的作用了。在本研究中,从 TCGA 和 GEO 数据库以及四川简阳人民医院病理科获得了 124 例 HCC 患者的 EWSR1 转录组和临床数据。Kaplan-Meier 和 Cox 回归分析用于评估患者的预后。TCGA 数据库分析显示,HCC 组织中 EWSR1 mRNA 水平显著高于正常肝组织(<0.001)。本研究队列的 TCGA 数据库分析表明,EWSR1 的上调与组织学分级、病理 T 分期和死亡有关,此外,在 EWSR1 过表达组中,T 分期、N 分期、TNM 分期、Ki67、AFP 表达均显著升高。单因素和多因素 Cox 风险回归分析结果表明,EWSR1 是 HCC 患者 OS 的独立预后因素,生物信息学分析表明,RNA 剪接过程是 EWSR1 的主要功能和途径。综上所述,我们的数据表明,EWSR1 可以作为 HCC 患者新的有前途的预后生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1652/8806985/72cd050f31d7/KBIE_A_1982844_F0001_OC.jpg

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