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Research Paper|Volume 14, Issue 19|pp 7774—7793

DNA methylation-regulated YTHDF2 correlates with cell migration and immune cell infiltration in glioma

Xiulin Jiang1, Xi Chen2, Xiaobin Huang2, Chunyan Wang3, Chenyang Wang3, Chenglong Pan3, William C. Cho4, Zhi Nie5, Jun Pu2, Weixiang Wang6
  • 1Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing 100049, China
  • 2Department of Neurosurgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, 650223, China
  • 3Department of Pathology, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan, China
  • 4Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong SAR, China
  • 5Department of Neurology, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan, China
  • 6Department of Clinical Laboratory, The People’s Hospital of Lishui, Lishui, Zhejiang 323000, China
* Equal contribution
Received: February 16, 2022Accepted: May 23, 2022Published: June 2, 2022
https://doi.org/10.18632/aging.204104

Copyright: © 2022 Jiang 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.

Abstract

Background: Glioma is a lethal malignant brain tumor, it comprises about 80% of all malignant brain tumours. Mounting evidence has reported that YTHDF2 plays a significant role in the cancer progression. However, the effects of YTHDF2 on the prognosis of low-grade gliomas (LGGs) and its correlation with tumor immune infiltration are unclear. The present study was designed to determine the biological functions of YTHDF2 in glioma and to evaluate the association of YTHDF2 expression with glioma progression.

Methods: Clinical data on patients with glioma were obtained from The Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA), the Gene Expression Omnibus (GEO), as well as the Rembrandt and Gravendeel databases. The correlations among YTHDF2 expression, pathological characteristics, glioma progression and clinical outcome were evaluated. In addition, the correlation of YTHDF2 expression with immune cell infiltration was analyzed too.

Results: We found that YTHDF2 was significantly up-regulated in LGGs which correlated with tumor grade and poor prognosis. Interestingly, we showed that YTHDF2 expression in LGG was associated with copy number variation, DNA hypomethylation, and induced transcription factor YY1. Besides, KEGG pathway analysis shows that YTHDF2 mainly participates in the immune response and oncogenic signaling pathway. Additionally, YTHDF2 is positively associated with diverse immune cells infiltration, immune cells, and multiple immune checkpoint molecules. Finally, we confirmed that YTHDF2 was highly expressed in LGGs tissues and correlated with the tumor grade with immunohistochemistry assay. More importantly, our results demonstrated that YTHDF2 was elevated in GBM cells. Knockdown of YTHDF2 significantly inhibits the proliferation and migration of GBM cells.

Conclusion: YTHDF2 correlates with glioma progression and immune cell infiltration, suggesting that YTHDF2 may be a useful prognostic biomarker for glioma.