Identification of CDKN3 overexpression as a marker of poor prognosis and potential therapeutic target in low-grade glioma
Abstract Low-grade glioma (LGG) is a primary, slow-growing brain tumor; however, its treatment and prognosis remain challenging. In this study, we analyzed cancer data from the TCGA database, focusing particularly on the expression of the CDKN3 gene in LGG. The results showed that high CDKN3 express...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-01-01
|
| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-025-86338-8 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832585870466613248 |
|---|---|
| author | Hongbing Cheng Xiao Meng Yanhua Zhang Pu Wang Yucheng Lu |
| author_facet | Hongbing Cheng Xiao Meng Yanhua Zhang Pu Wang Yucheng Lu |
| author_sort | Hongbing Cheng |
| collection | DOAJ |
| description | Abstract Low-grade glioma (LGG) is a primary, slow-growing brain tumor; however, its treatment and prognosis remain challenging. In this study, we analyzed cancer data from the TCGA database, focusing particularly on the expression of the CDKN3 gene in LGG. The results showed that high CDKN3 expression in LGG patients was significantly associated with poor survival outcomes. Further gene expression analysis revealed that 379 genes were significantly upregulated in LGG samples with high CDKN3 expression, and these genes were primarily involved in the mitotic cell cycle and extracellular matrix organization. Additionally, high CDKN3 expression was closely linked to key signaling pathways such as tumor inflammation, hypoxic response, and tumor proliferation. Immune microenvironment analysis showed that high CDKN3 expression significantly increased the expression of CD4 + T cells and specific immune checkpoint genes, suggesting a potentially poor response to immune checkpoint blockade therapy. Through in vitro and in vivo experiments, we confirmed that CDKN3 silencing significantly inhibited the proliferative capacity of LGG cells. Proteomics revealed that CDKN3 can bind ARG1 and inhibite the intracellular arginase activity. These findings not only improve our understanding of LGG biology but also provide scientific evidence for developing potential therapeutic strategies targeting CDKN3. |
| format | Article |
| id | doaj-art-ba7132f0dd8944e6908d6240254b4ca8 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-ba7132f0dd8944e6908d6240254b4ca82025-01-26T12:27:58ZengNature PortfolioScientific Reports2045-23222025-01-0115111510.1038/s41598-025-86338-8Identification of CDKN3 overexpression as a marker of poor prognosis and potential therapeutic target in low-grade gliomaHongbing Cheng0Xiao Meng1Yanhua Zhang2Pu Wang3Yucheng Lu4Shanxi Key Laboratory of Aging Mechanism Research and Translational Applications, Changzhi Medical CollegeDepartment of Basic Medicine, Changzhi Medical CollegeDepartment of Cardiology, The Third People’s Hospital of DatongShanxi Key Laboratory of Aging Mechanism Research and Translational Applications, Changzhi Medical CollegeBiobank, Linyi People’s HospitalAbstract Low-grade glioma (LGG) is a primary, slow-growing brain tumor; however, its treatment and prognosis remain challenging. In this study, we analyzed cancer data from the TCGA database, focusing particularly on the expression of the CDKN3 gene in LGG. The results showed that high CDKN3 expression in LGG patients was significantly associated with poor survival outcomes. Further gene expression analysis revealed that 379 genes were significantly upregulated in LGG samples with high CDKN3 expression, and these genes were primarily involved in the mitotic cell cycle and extracellular matrix organization. Additionally, high CDKN3 expression was closely linked to key signaling pathways such as tumor inflammation, hypoxic response, and tumor proliferation. Immune microenvironment analysis showed that high CDKN3 expression significantly increased the expression of CD4 + T cells and specific immune checkpoint genes, suggesting a potentially poor response to immune checkpoint blockade therapy. Through in vitro and in vivo experiments, we confirmed that CDKN3 silencing significantly inhibited the proliferative capacity of LGG cells. Proteomics revealed that CDKN3 can bind ARG1 and inhibite the intracellular arginase activity. These findings not only improve our understanding of LGG biology but also provide scientific evidence for developing potential therapeutic strategies targeting CDKN3.https://doi.org/10.1038/s41598-025-86338-8Low-grade gliomaCDKN3PrognosisImmune infiltration |
| spellingShingle | Hongbing Cheng Xiao Meng Yanhua Zhang Pu Wang Yucheng Lu Identification of CDKN3 overexpression as a marker of poor prognosis and potential therapeutic target in low-grade glioma Scientific Reports Low-grade glioma CDKN3 Prognosis Immune infiltration |
| title | Identification of CDKN3 overexpression as a marker of poor prognosis and potential therapeutic target in low-grade glioma |
| title_full | Identification of CDKN3 overexpression as a marker of poor prognosis and potential therapeutic target in low-grade glioma |
| title_fullStr | Identification of CDKN3 overexpression as a marker of poor prognosis and potential therapeutic target in low-grade glioma |
| title_full_unstemmed | Identification of CDKN3 overexpression as a marker of poor prognosis and potential therapeutic target in low-grade glioma |
| title_short | Identification of CDKN3 overexpression as a marker of poor prognosis and potential therapeutic target in low-grade glioma |
| title_sort | identification of cdkn3 overexpression as a marker of poor prognosis and potential therapeutic target in low grade glioma |
| topic | Low-grade glioma CDKN3 Prognosis Immune infiltration |
| url | https://doi.org/10.1038/s41598-025-86338-8 |
| work_keys_str_mv | AT hongbingcheng identificationofcdkn3overexpressionasamarkerofpoorprognosisandpotentialtherapeutictargetinlowgradeglioma AT xiaomeng identificationofcdkn3overexpressionasamarkerofpoorprognosisandpotentialtherapeutictargetinlowgradeglioma AT yanhuazhang identificationofcdkn3overexpressionasamarkerofpoorprognosisandpotentialtherapeutictargetinlowgradeglioma AT puwang identificationofcdkn3overexpressionasamarkerofpoorprognosisandpotentialtherapeutictargetinlowgradeglioma AT yuchenglu identificationofcdkn3overexpressionasamarkerofpoorprognosisandpotentialtherapeutictargetinlowgradeglioma |