Research Paper Volume 14, Issue 23 pp 9632—9646

Upregulated UBE4B expression correlates with poor prognosis and tumor immune infiltration in hepatocellular carcinoma

Xuyang Shao1,2, *,#, , Jun Zhu3, *,#, , Yanlong Shi4, *,#, , Hanlu Fang5, *,#, , Jingsi Chen6, *,#, , Yixiao Zhang7, *,#, , Jingyan Wang8, , Haokun Jian9, , Sheng Lan10, , Fei Jiang11, , Fei Zhong3,12, , Yewei Zhang4, , Chenxi Cao1,2, ,

  • 1 Graduate School of Bengbu Medical College, Bengbu 233000, Anhui Province, China
  • 2 Department of General Surgery, The Second Affiliated Hospital of Jiaxing University, Jiaxing 314000, Zhejiang Province, China
  • 3 Department of Oncology, Fuyang Hospital of Anhui Medical University, Fuyang 236000, Anhui Province, China
  • 4 Hepatopancreatobiliary Center, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210003, Jiangsu Province, China
  • 5 Institute of Medical and Health Science of HeBMU, Hebei Medical University, Shijiazhuang 050017, Hebei Province, China
  • 6 Department of Intensive Care Unit, Fuyang Women and Children’s Hospital, Fuyang 236000, Anhui Province, China
  • 7 The First Clinical College of Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang Province, China
  • 8 Department of Anesthesia, Shaoxing People’s Hospital, Shaoxing 312000, Zhejiang Province, China
  • 9 School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang 453003, Henan Province, China
  • 10 The Second Clinical College of Guangzhou Medical University, Guangzhou 510030, Guangdong Province, China
  • 11 Department of General Surgery, Fuyang Hospital of Anhui Medical University, Fuyang 236000, Anhui Province, China
  • 12 Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei 230000, Anhui Province, China
* Equal contribution
# Share first authorship

Received: October 17, 2022       Accepted: November 23, 2022       Published: December 5, 2022
How to Cite

Copyright: © 2022 Shao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Background: Hepatocellular carcinoma (HCC) is a major human health concern. Increasing evidence has demonstrated that ubiquitin ligase E4B (UBE4B) may be involved in the occurrence and development of various human cancers and may affect prognosis. However, the specific role and mechanism of UBE4B in HCC is unclear.

Methods: A pan-cancer analysis of UBE4B expression, clinicopathological features, and prognosis was performed using bioinformatics techniques. Subsequently, the expression, prognosis, and correlation of UBE4B and its upstream miRNAs and lncRNAs were analyzed. We investigated the relationship between UBE4B expression and immune cell infiltration, immunomodulatory factors, and chemokines in HCC. The expression levels of UBE4B and its upstream lncRNAs (FGD5-AS1, LINC00858, and SNHG16) and miRNAs (hsa-miR-22-3p) were evaluated in HCC cell lines using qRT-PCR.

Results: UBE4B expression increased in HCC and was correlated with a poor survival rate in patients with HCC. A ceRNA network was established to identify the UBE4B-hsa-miR-22-3p-FGD5-AS1/LINC00858/SNHG16 regulatory axis in HCC. UBE4B expression was significantly associated with immune cell infiltration, immunomodulators, chemokines, and their receptors in HCC. The mRNA expression of FGD5-AS1, LINC00858, SNHG16, and UBE4B was higher in the HCC cell lines (7721 and HepG2) than in the normal hepatocyte line (LO2), and the expression of hsa-miR-22-3p mRNA showed a decreasing trend.

Conclusions: Our findings showed that upregulation of UBE4B was associated with poor prognosis and tumor immune infiltration in HCC. These findings will aid in understanding the relevant functions of UBE4B and provide new strategies for drug development and exploration of prognosis-related biomarkers.


HCC: Hepatocellular carcinoma; UBE4B: Ubiquitin ligase E4B; HBV: Hepatitis B virus; HCV: Hepatitis C virus; PTMs: Post-translational modifications; UPS: Ubiquitin-proteasome system; TCGA: The Cancer Genome Atlas; GTEx: The Genotype-Tissue Expression; TIMER: Tumor Immune Estimation Resource; GEPIA: Gene Expression Profiling Interactive Analysis; OS: Overall survival; RFS: Recurrence-free survival; HRs: Hazard ratios; CIs: Confidence intervals; CeRNA: Competing Endogenous RNAs; qRT-PCR: Quantitative real-time PCR; HPA: Human Protein Atlas.