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高表达的CENPL与乳腺癌细胞增殖和免疫浸润相关。

Highly expressed CENPL is correlated with breast cancer cell proliferation and immune infiltration.

作者信息

Gui Zhengwei, Tian Yao, Liu Shiyang, Yu Tianyao, Liu Chenguang, Zhang Lin

机构信息

Department of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

出版信息

Front Oncol. 2023 Feb 2;13:1046774. doi: 10.3389/fonc.2023.1046774. eCollection 2023.

Abstract

BACKGROUND

Centromere protein L (CENPL) is associated with a variety of human diseases. However, its function in breast cancer remains uncertain.

METHODS

The Cancer Genome Atlas (TCGA) and genotype-tissue expression across cancer data were used to investigate CENPL expression. Using TCGA clinical survival data, the relationship between CENPL expression and patient prognosis was assessed. Using the cluster profiler R software tool, enrichment analysis of CENPL was carried out. Additionally, by studying the TCGA database, the relationship between CENPL expression and immune cell infiltration was assessed. To evaluate CENPL's impact on breast cancer cell proliferation, the CCK8 test and colony-formation assay were carried out. Scratch testing and the transwell assay were used to evaluate the effects of CENPL on breast cancer cell migration.

RESULTS

Breast cancer was one of numerous tumor forms with high CENPL expression. Significant relationships between high CENPL expression and the cell cycle, nuclear division, organelle fission, and chromosome segregation were found. Further investigation revealed that minimal infiltration of CD8-positive T cells and natural killer (NK) cells and high levels of Tregs and macrophages were correlated with high levels of CENPL expression. CENPL expression was linked to more than half of the ICP genes. Breast cancer cells' ability to proliferate and migrate was decreased by CENPL knockdown.

CONCLUSIONS

Our findings suggest that CENPL may be an oncogene in breast cancer and a predictor of efficacy of immunotherapy for breast cancer.

摘要

背景

着丝粒蛋白L(CENPL)与多种人类疾病相关。然而,其在乳腺癌中的功能仍不确定。

方法

利用癌症基因组图谱(TCGA)和跨癌症数据的基因型-组织表达来研究CENPL的表达。使用TCGA临床生存数据,评估CENPL表达与患者预后之间的关系。使用聚类分析R软件工具对CENPL进行富集分析。此外,通过研究TCGA数据库,评估CENPL表达与免疫细胞浸润之间的关系。为评估CENPL对乳腺癌细胞增殖的影响,进行了CCK8试验和集落形成试验。划痕试验和Transwell试验用于评估CENPL对乳腺癌细胞迁移的影响。

结果

乳腺癌是CENPL表达较高的众多肿瘤类型之一。发现CENPL高表达与细胞周期、核分裂、细胞器分裂和染色体分离之间存在显著关系。进一步研究表明,CD8阳性T细胞和自然杀伤(NK)细胞的低浸润以及调节性T细胞(Tregs)和巨噬细胞的高水平与CENPL高表达相关。CENPL表达与一半以上的免疫检查点(ICP)基因相关。CENPL敲低降低了乳腺癌细胞的增殖和迁移能力。

结论

我们的研究结果表明,CENPL可能是乳腺癌中的一种癌基因,也是乳腺癌免疫治疗疗效的预测指标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ded/9932532/3fcf1da194e2/fonc-13-1046774-g001.jpg

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