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

Abstract

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 (P < 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. Abbreviations: 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.