Zheng Qiuxian, Fu Qiang, Xu Jia, Gu Xinyu, Zhou Haibo, Zhi Chen
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China.
School of Continuing Education, Zhejiang University, Hangzhou 310003, China.
J Cancer. 2021 Jan 21;12(6):1792-1803. doi: 10.7150/jca.51616. eCollection 2021.
Recent studies have shown that the transcription factor E2F4 is involved in the progression of various tumors, but its expression and influence on immune cell infiltration and biological functions are largely unknown in hepatocellular carcinoma (HCC). The Cancer Genome Atlas (TCGA) database, the Tumor Immune Estimation Resource (TIMER) and related online tools as well as a tissue microarray (TMA) were used for analyses in our study. E2F4 expression was elevated in HCC tumor tissue compared with adjacent normal tissue at both the mRNA and protein levels. Overexpression of E2F4 was markedly related to a poor prognosis in HCC patients. In addition, positively and negatively correlated significant genes of E2F4 were identified in HCC. Pathway enrichment analyses revealed that the top 100 positively correlated significant genes of E2F4 were closely related to nuclear splicing and degradation-related pathways. Furthermore, nine hub genes correlated with E2F4 expression were validated based on a protein-protein interaction (PPI) network. It was also demonstrated that E2F4 expression was negatively correlated to immune purity and positively correlated to immune cell infiltration. E2F4 could serve as a novel biomarker for HCC diagnosis and prognosis prediction.
近期研究表明,转录因子E2F4参与多种肿瘤的进展,但其在肝细胞癌(HCC)中的表达以及对免疫细胞浸润和生物学功能的影响在很大程度上尚不清楚。本研究使用癌症基因组图谱(TCGA)数据库、肿瘤免疫评估资源(TIMER)及相关在线工具以及组织芯片(TMA)进行分析。与相邻正常组织相比,HCC肿瘤组织中E2F4在mRNA和蛋白质水平的表达均升高。E2F4的过表达与HCC患者的不良预后显著相关。此外,在HCC中鉴定出了与E2F4呈正相关和负相关的显著基因。通路富集分析显示,E2F4的前100个正相关显著基因与核剪接和降解相关通路密切相关。此外,基于蛋白质-蛋白质相互作用(PPI)网络验证了9个与E2F4表达相关的枢纽基因。研究还表明,E2F4表达与免疫纯度呈负相关,与免疫细胞浸润呈正相关。E2F4可作为HCC诊断和预后预测的新型生物标志物。