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综合分析表明,PLK3是胶质瘤中一个有前景的免疫靶点和预后指标。

Comprehensive analysis reveals PLK3 as a promising immune target and prognostic indicator in glioma.

作者信息

Zhu Tianyun, Zhao Cunyan, Gong Rui, Qian A O, Wang Xiaoshu, Lu Fanghui, Huo Gang, Qiao Liangjun, Chen Song

机构信息

Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.

Institute of Life Sciences, Chongqing Medical University, Chongqing, 400016, China.

出版信息

Oncol Res. 2025 Jan 16;33(2):431-442. doi: 10.32604/or.2024.050794. eCollection 2025.

Abstract

BACKGROUND

PLK3, which played an important role in cell cycle progression and stress response, was identified as highly expressed in various carcinomas. However, the functions, molecular characteristics, and prognostic value of PLK3 in glioma remained unexplored.

METHODS

We analyzed PLK3 expression in glioma samples from multiple databases. Both overexpression and knockdown of Plk3 were performed to investigate tumor cell growth in glioma, and the transplanted glioma mouse model demonstrated the role of Plk3 on tumor progression. Immunohistochemistry was conducted to detect PLK3 expression and immune cell infiltration. The trans-well assay for PLK3 on the immune cells recruitment was also determined. Additionally, we further evaluated the correlation between PLK3 and PD-1/PD-L1 as well as other immune checkpoints.

RESULTS

We found that an increased level of PLK3 was associated with malignancy and poor prognosis of glioma, and further validated that PLK3 promoted glioma progression. PLK3 also played a crucial role in immune response and was involved in Tcell immune suppression. Specifically, we revealed that CD8 and CD4 Tcell infiltration was decreased in Plk3 overexpressed xenografts. Furthermore, it was predicted that PLK3 was synergistic with other checkpoint members in glioma. In general, high expression of PLK3 was associated with a malignant process and poor prognosis in glioma patients.

CONCLUSION

Our findings indicated that PLK3 expression level was highly correlated to the malignancy of gliomas, and we validated that PLK3 could promote the GBM progress and . Furthermore, PLK3 played important roles in Tcell and neutrophil immune response in glioma. Besides, the conspicuous association between PLK3 and other immune checkpoints was also observed. Crucially, high-level PLK3 expression was revealed to be related to poor clinical prognosis. These results demonstrated that PLK3 may serve as a prognostic biomarker and a potential target for glioma.

摘要

背景

PLK3在细胞周期进程和应激反应中发挥重要作用,已被确定在多种癌症中高表达。然而,PLK3在胶质瘤中的功能、分子特征和预后价值仍未得到探索。

方法

我们分析了多个数据库中胶质瘤样本的PLK3表达情况。进行了Plk3的过表达和敲低实验,以研究其对胶质瘤肿瘤细胞生长的影响,并且移植性胶质瘤小鼠模型证明了Plk3在肿瘤进展中的作用。进行免疫组织化学检测PLK3表达和免疫细胞浸润情况。还通过Transwell实验测定了PLK3对免疫细胞招募的影响。此外,我们进一步评估了PLK3与PD-1/PD-L1以及其他免疫检查点之间的相关性。

结果

我们发现PLK3水平升高与胶质瘤的恶性程度和不良预后相关,并进一步验证了PLK3促进胶质瘤进展。PLK3在免疫反应中也起着关键作用,并参与T细胞免疫抑制。具体而言,我们发现Plk3过表达的异种移植瘤中CD8和CD4 T细胞浸润减少。此外,预测PLK3在胶质瘤中与其他检查点成员具有协同作用。总体而言,PLK3高表达与胶质瘤患者的恶性进程和不良预后相关。

结论

我们的研究结果表明,PLK3表达水平与胶质瘤的恶性程度高度相关,并且我们验证了PLK3可以促进胶质母细胞瘤进展。此外,PLK3在胶质瘤的T细胞和中性粒细胞免疫反应中发挥重要作用。此外,还观察到PLK3与其他免疫检查点之间存在明显关联。至关重要的是,高水平的PLK3表达与不良临床预后相关。这些结果表明,PLK3可能作为胶质瘤的预后生物标志物和潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3b0/11753997/4bebe53c2c7e/OncolRes-33-50794-f001.jpg

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