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PRIM2: A Marker of MYC-driven Hyper-proliferation, Disease Progression, Tumor Aggressiveness and Poor Survival in Glioma Patients.


ABSTRACT:

Background/aim

Gliomas are the most prevalent brain tumors with metabolic alterations playing a pivotal role in disease progression. However, the precise coordination of metabolic alterations with tumor-promoting cellular mechanisms, leading to tumor initiation, progression, and aggressiveness, resulting in poor outcomes, remains poorly understood in gliomas.

Materials and methods

We conducted a metabolism-targeted differential gene expression analysis using glioma patients' expression profiling data from The Cancer Genome Atlas (TCGA) database. In addition, pathway enrichment analysis, gene set enrichment analysis (GSEA), transcription factor prediction, network construction, and correlation analyses were performed. Survival analyses were performed in R. All results were validated using independent GEO expression datasets.

Results

Metabolism-targeted analysis identified 5 hits involved in diverse metabolic processes linking them to disease aggressiveness in gliomas. Subsequently, we established that cell cycle progression and hyper-proliferation are key drivers of tumor progression and aggressiveness in gliomas. One of the identified metabolic hits, DNA primase 2 (PRIM2), a gene involved in DNA replication was found directly associated with cell cycle progression in gliomas. Furthermore, our analysis indicated that PRIM2, along with other cell cycle-related genes, is under the control of and regulated by the oncogenic MYC transcription factor in gliomas. In addition, PRIM2 expression alone is enough to predict MYC-driven cell cycle progression and is associated with tumor progression, aggressive disease state, and poor survival in glioma patients.

Conclusion

Our findings highlight PRIM2 as a marker of MYC-driven cell cycle progression and hyper-proliferation, disease onset and progression, tumor aggressiveness, and poor survival in glioma patients.

SUBMITTER: Sun R 

PROVIDER: S-EPMC10905270 | biostudies-literature | 2024 Mar-Apr

REPOSITORIES: biostudies-literature

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PRIM2: A Marker of MYC-driven Hyper-proliferation, Disease Progression, Tumor Aggressiveness and Poor Survival in Glioma Patients.

Sun Ronghui R   Shao Xiaodong X   Akter Farhana F   Zahid Kashif Rafiq KR   Yao Shun S   Ma Lianting L   Xu Guozheng G  

Cancer genomics & proteomics 20240301 2


<h4>Background/aim</h4>Gliomas are the most prevalent brain tumors with metabolic alterations playing a pivotal role in disease progression. However, the precise coordination of metabolic alterations with tumor-promoting cellular mechanisms, leading to tumor initiation, progression, and aggressiveness, resulting in poor outcomes, remains poorly understood in gliomas.<h4>Materials and methods</h4>We conducted a metabolism-targeted differential gene expression analysis using glioma patients' expre  ...[more]

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