Abstract
Lower-grade gliomas (LGGs) are slow-growing, indolent tumors that usually affect younger patients and present a therapeutic challenge due to the heterogeneity of their clinical presentation. Dysregulation of cell cycle regulatory factors is implicated in the progression of many tumors, and drugs that target cell cycle machinery have shown efficacy as promising therapeutic approaches. To date, however, no comprehensive study has examined how cell cycle-related genes affect LGG outcomes. The cancer genome atlas (TCGA) data were used as the training set for differential analysis of gene expression and patient outcomes; the Chinese glioma genome atlas (CGGA) was used for validation. Levels of one candidate protein, cyclin-dependent kinase inhibitor 2C (CDKN2C), and its relationship to clinical prognosis were determined using a tissue microarray containing 34 LGG tumors. A nomogram was constructed to model the putative role of candidate factors in LGG. Cell type proportion analysis was performed to evaluate immune cell infiltration in LGG. Various genes encoding cell cycle regulatory factors showed increased expression in LGG and were significantly related to isocitrate dehydrogenase and chromosome arms 1p and 19q mutation status. CDKN2C expression independently predicted the outcome of LGG patients. High M2 macrophage values along with elevated CDKN2C expression were associated with poorer prognosis in LGG patients. CDKN2C plays an oncogenic role in LGG, which is associated with M2 macrophages.
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This work was Sponsored by Shanghai Sailing Program (20YF1427000) and Ruijin Youth NSCF Cultivation Fund (KY20194238).
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All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Qiongni Zhu, Zhimin Zhu, Lei Hu, and Ying Guo. The first draft of the manuscript was written by Qiongni Zhu and Lei Hu. Writing review and editing of the manuscript were done by Stephen James Renaud and Ying Guo. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
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Zhu, Q., Zhu, Z., Renaud, S.J. et al. The Oncogenic Role of Cyclin-Dependent Kinase Inhibitor 2C in Lower-Grade Glioma. J Mol Neurosci 73, 327–344 (2023). https://doi.org/10.1007/s12031-023-02120-3
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DOI: https://doi.org/10.1007/s12031-023-02120-3