Yu Bin, Liang Han, Ye Qifa, Wang Yanfeng
Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan, China.
The 3rd Xiangya Hospital of Central South University, Research Center of National Health Ministry on Transplantation Medicine Engineering and Technology, Changsha, China.
J Gastrointest Oncol. 2020 Oct;11(5):1009-1023. doi: 10.21037/jgo-20-192.
The oncogenic role of excision repair cross-complementation group 6-like (ERCC6L) has been revealed in several cancers recently, but little is known about its expression and function in hepatocellular carcinoma (HCC).
Utilizing public data from Human Protein Atlas (HPA) and The Cancer Genome Atlas (TCGA) databases, ERCC6L dysregulation in HCC and its clinical significance were determined by -test and Chi-square test. Comprehensive survival analyses (such as nomogram, Cox regression model and Kaplan-Meier analysis) were performed to assess prognostic value of ERCC6L for HCC patients. Integrated bioinformatics analyses [including copy number alterations (CNA), DNA methylation, miRNA prediction and gene set enrichment analysis (GSEA)] were conducted to explore the mechanisms and biological roles underlying ERCC6L dysregulation in HCC.
ERCC6L upregulation was identified in HCC tissues compared to normal controls (P<0.05). In addition, overexpression of ERCC6L not only correlated with elevated alpha fetoprotein (AFP), vascular invasion (VI), and advanced histologic grade and TNM stage, but also had an independent prognostic value for the poorer overall survival (OS) and recurrence-free survival (RFS) of HCC patients (all P<0.05). Besides, nomogram integrating ERCC6L expression and TNM stage showed superior prognostic ability than that of TNM stage (P<0.05). Moreover, ERCC6L promoter hypomethylation and miR-5589 downregulation in HCC might result in ERCC6L overexpression (all P<0.05). Furthermore, eight biological pathways (including the DNA replication, cell cycle and p53 pathways) related to ERCC6L upregulation in HCC were found to be enriched by GSEA, and ERCC6L upregulation was positively correlated with PLK1 (polo-like kinase 1) expression and TP53 mutation in HCC, which preliminarily shed light on the roles of ERCC6L in HCC.
ERCC6L may serve as a promising prognostic indicator and therapeutic target for HCC patients.
切除修复交叉互补组6样蛋白（ERCC6L）的致癌作用最近在几种癌症中已被揭示，但对其在肝细胞癌（HCC）中的表达和功能知之甚少。
利用来自人类蛋白质图谱（HPA）和癌症基因组图谱（TCGA）数据库的公开数据，通过t检验和卡方检验确定HCC中ERCC6L的失调及其临床意义。进行综合生存分析（如列线图、Cox回归模型和Kaplan-Meier分析）以评估ERCC6L对HCC患者的预后价值。进行综合生物信息学分析[包括拷贝数改变（CNA）、DNA甲基化、miRNA预测和基因集富集分析（GSEA）]以探索HCC中ERCC6L失调的机制和生物学作用。
与正常对照相比，HCC组织中鉴定出ERCC6L上调（P<0.05）。此外，ERCC6L的过表达不仅与甲胎蛋白（AFP）升高、血管侵犯（VI）以及高级别组织学分级和TNM分期相关，而且对HCC患者较差的总生存期（OS）和无复发生存期（RFS）具有独立的预后价值（所有P<0.05）。此外，整合ERCC6L表达和TNM分期的列线图显示出比TNM分期更好的预后能力（P<0.05）。此外，HCC中ERCC6L启动子低甲基化和miR-5589下调可能导致ERCC6L过表达（所有P<0.05）。此外，通过GSEA发现HCC中与ERCC6L上调相关的八个生物学途径（包括DNA复制、细胞周期和p53途径）被富集，并且ERCC6L上调与HCC中PLK1（polo样激酶1）表达和TP53突变呈正相关，这初步揭示了ERCC6L在HCC中的作用。
ERCC6L可能是HCC患者一个有前景的预后指标和治疗靶点。
