Research Paper Volume 15, Issue 9 pp 3690—3714
MGME1 associates with poor prognosis and is vital for cell proliferation in lower-grade glioma
- 1 Departments of Neurosurgery, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, China
- 2 Jiangxi Key Laboratory of Neurological Tumors and Cerebrovascular Diseases, Nanchang 330006, Jiangxi, China
- 3 Jiangxi Health Commission Key Laboratory of Neurological Medicine, Nanchang 330006, Jiangxi, China
- 4 Institute of Neuroscience, Nanchang University, Nanchang 330006, Jiangxi, China
- 5 Department of Respiratory Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang 330030, Jiangxi, China
- 6 Department of Operation, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, China
Received: February 6, 2023 Accepted: April 18, 2023 Published: May 8, 2023
https://doi.org/10.18632/aging.204705How to Cite
Copyright: © 2023 Xiao 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
Objective: Mitochondrial genome maintenance exonuclease 1 (MGME1) is associated with DNA depletion, deletion, duplication, and rearrangement. However, the function of MGME1 in tumors, especially lower-grade gliomas (LGGs), has not been established.
Methods: Pan-cancer analysis was used to define the expression patterns and prognostic value of MGME1 in various cancers. Subsequently, we systematically determined the associations between MGME1 expression and clinicopathological characteristics, prognosis, biological functions, immune characteristics, genomic mutations, and therapeutic responses of LGGs based on their expression patterns. The expression level and specific functions of MGME1 in LGGs was detected by conducting in vitro experiments.
Results: Abnormally enhanced and high MGME1 expressions were associated with poor prognoses of various tumors, including LGG. Multivariate and univariate Cox regression analyses manifested that MGME1 expression was an independent prognostic biomarker for LGG. The immune-related signatures, infiltration of immune cells, immune checkpoint genes (ICPGs), copy number alteration (CNA), tumor mutation burden (TMB), and treatment responses of LGG patients were associated with the expression of MGME1. The in vitro experiments affirmed that MGME1 was elevated and tightly connected with the cell proliferation and cell cycle in LGG.
Conclusions: MGME1 is an independent prognostic biomarker and closely related to the cell proliferation in LGG.
Abbreviations
MGME1: mitochondrial genome maintenance exonuclease 1; LGG: lower-grade glioma; ICPGs: immune checkpoint genes; CNA: copy number alteration; TMB: tumor mutation burden; WHO: World Health Organization; TCGA: The Cancer Genome Atlas; CGGA: Chinese Glioma Genome Atlas; IDH: isocitrate dehydrogenase; ssGSEA: single-sample GSEA; TIICs: tumor-infiltrating immune cells; DSS: disease special survival; GTEx: Genotypic-Tissue Expression; FPKM: Fragments Per Kilobase Million; TPM: transcripts per kilobase million; OS: overall survival; ROC: receiver operating characteristics; AUC: area under the curve; FDR: false-discovery rate; DEGs: differentially expressed genes; GO-BP: Gene Ontology Biological Process; KEGG: Kyoto Encyclopedia of Genes and Genomes; NHA: normal human astrocyte; ATCC: American Type Culture Collection; NC: negative control; MOIs: multiplicities of infection; PVDF: transferred it to polyvinylidene fluoride; ECL: enhanced chemiluminescence; IC50: lower inhibitory centration; qRT-PCR: quantitative Real-Time PCR.