J Cancer 2021; 12(6):1792-1803. doi:10.7150/jca.51616

Research Paper

Transcription factor E2F4 is an indicator of poor prognosis and is related to immune infiltration in hepatocellular carcinoma

Qiuxian Zheng1*, Qiang Fu2*, Jia Xu1*, Xinyu Gu1, Haibo Zhou1, Chen Zhi1✉

1. 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.
2. School of Continuing Education, Zhejiang University, Hangzhou 310003, China.
*These authors contributed equally to this work.

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Citation:
Zheng Q, Fu Q, Xu J, Gu X, Zhou H, Zhi C. Transcription factor E2F4 is an indicator of poor prognosis and is related to immune infiltration in hepatocellular carcinoma. J Cancer 2021; 12(6):1792-1803. doi:10.7150/jca.51616. Available from https://www.jcancer.org/v12p1792.htm

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Abstract

Background: 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).

Methods: 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.

Results: 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.

Conclusion: E2F4 could serve as a novel biomarker for HCC diagnosis and prognosis prediction.

Keywords: HCC, E2F4, hub genes, prognosis, immune infiltration