Research Paper Volume 16, Issue 7 pp 6188—6211

Potential value of expression of receptor accessory protein 4 for evaluating the prognosis of lower-grade glioma patients

Shuping Luo1, *, , Zhendong Liu2, *, , Haigang Chang3, *, , Xingbo Cheng2, , Rongjun Qian4, , Yanzheng Gao2, , Chaofeng Hou1, ,

  • 1 Department of Colorectal Surgery, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, Henan, China
  • 2 Department of Surgery of Spine and Spinal Cord, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, People’s Hospital of Henan University, Zhengzhou 450003, Henan, China
  • 3 Department of Neurosurgery, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan, China
  • 4 Department of Neurosurgery, Henan Provincial People’s Hospital, People’s Hospital of Henan University, People’s Hospital of Zhengzhou University, Zhengzhou 450003, Henan, China
* Equal contribution

Received: December 16, 2023       Accepted: December 18, 2023       Published: March 28, 2024
How to Cite

Copyright: © 2024 Luo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Background: REEP4 is involved in the regulation of the biological process of mitosis. Lower grade glioma (LGG), as a malignant tumor, is accompanied by abnormalities in mitosis, but there have been no reports of REEP4 so far.

Methods: We collected transcriptome data, DNA methylation data and the clinical characteristics of thousands of patients with LGG. Various big data analysis methods and molecular biology experiments were employed to reveal the impact of REEP4 on the pathological process of LGG.

Results: It was found that the expression of REEP4 was significantly elevated and negatively regulated by its methylation site. Therefore, both the high expression of REEP4 and low methylation state of cg16311504 showed that the patients are correlated with lower patient survival rate. In addition, high REEP4 expression participates in the regulation of various cancer-related cellular signaling pathways, such as the cell cycle, MAPK signaling pathway, NOD-like receptor signaling pathway, etc. More importantly, the level of immune cell infiltration significantly increased in the high expression group of REEP4 in the LGG tumor microenvironment and REEP4 has a high positive correlation with PD-L1 and other immune checkpoints.

Conclusions: In brief, this study is the first to introduce REEP4 in malignant tumors, which can be used as an independent risk factor that participates in the malignant process of LGG. More importantly, REEP4 has the potential to become a new star in the field of anti-tumor treatment.


LGG: lower-grade glioma; CTLA4: cytotoxic T lymphocyte antigen 4; ICIs: immune checkpoint inhibitors; NPCs: nuclear pore complexes; GEPIA: Gene Expression Profiling Interactive Analysis; TCGA: The Cancer Genome Atlas; HA: human astrocyte; FBS: fetal bovine serum; TD-ROC: time-dependent receiver operating characteristic; IDH: isocitrate dehydrogenase.