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3级胶质瘤患者中CREBBP和EP300的表达与肿瘤体积的相关性:一项回顾性分析

Expression of CREBBP and EP300 Associated With Tumor Volume in Patients With Grade-3 Glioma: A Retrospective Analysis.

作者信息

Chen Cuiwei, Yuan Meiqin, Xia Liang, Wu Xin, Zhong Xingguang, Zhang Huangjie, Zhang Lidan, Liu Xuan, Wang Zeng, Sun Caixing

机构信息

Department of Pharmacy, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China.

School of Medicine, Zhejiang University, Hangzhou, China.

出版信息

Clin Med Insights Oncol. 2024 Oct 16;18:11795549241287777. doi: 10.1177/11795549241287777. eCollection 2024.

DOI:10.1177/11795549241287777
PMID:39429683
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11490948/
Abstract

BACKGROUND

Reliable predictive data are crucial for making accurate treatment decisions in glioma patients, but it can be challenging to obtain due to limited information in many cases. Numerous research studies have indicated the involvement of cyclic adenosine monophosphate (cAMP)-response element binding protein (CREBBP) and E1A binding protein p300 (EP300) in tumorigenesis and tumor progression across various types.

METHODS

The messenger RNA (mRNA) expression levels of CREBBP and EP300 were retrospectively analyzed in 17 grade-3 glioma patients. The SYBR Green real-time polymerase chain reaction (RT-PCR) technique was employed for mRNA expression analysis, with the glyceraldehyde-3-phosphate dehydrogenase gene () used as a reference gene for data normalization. In addition, the relationship between CREBBP, EP300 expression and patients' clinical information, imaging features, histologic features, immune factors, and overall survival was assessed through univariate analyses.

RESULTS

The analysis of the data unveiled a statistically significant upregulation of CREBBP and EP300 mRNA expression levels in large gliomas as compared with their smaller counterparts ( < .05). Histological examination using hematoxylin and eosin (H&E) staining exhibited marked cellular heterogeneity, with heightened cell density observed specifically within tumors displaying elevated CREBBP expression levels. In contrast, there was a substantial downregulation of complement 3 and complement 4 within larger tumor volumes when compared with smaller ones ( < .05). However, these findings do not serve as clinically relevant prognostic indicators for glioma.

CONCLUSIONS

It is suggested that higher expression levels of CREBBP and EP300 are positively associated with increased tumor volume. Inhibition of CREBBP and EP300 enhances local immunogenicity, leading to the recruitment of immune cells and release of cytokines for effective tumor eradication, ultimately resulting in the inhibition of tumor growth.

摘要

背景

可靠的预测数据对于胶质瘤患者做出准确的治疗决策至关重要,但在许多情况下,由于信息有限,获取这些数据可能具有挑战性。大量研究表明,环磷酸腺苷(cAMP)反应元件结合蛋白(CREBBP)和E1A结合蛋白p300(EP300)参与了多种类型肿瘤的发生和进展。

方法

回顾性分析17例3级胶质瘤患者中CREBBP和EP300的信使核糖核酸(mRNA)表达水平。采用SYBR Green实时聚合酶链反应(RT-PCR)技术进行mRNA表达分析,以甘油醛-3-磷酸脱氢酶基因()作为数据标准化的参考基因。此外,通过单因素分析评估CREBBP、EP300表达与患者临床信息、影像学特征、组织学特征、免疫因子和总生存期之间的关系。

结果

数据分析显示,与较小的胶质瘤相比,较大胶质瘤中CREBBP和EP300 mRNA表达水平在统计学上显著上调(P<0.05)。苏木精和伊红(H&E)染色的组织学检查显示出明显的细胞异质性,特别是在CREBBP表达水平升高的肿瘤中观察到细胞密度增加。相比之下,与较小肿瘤体积相比,较大肿瘤体积内补体3和补体4显著下调(P<0.05)。然而,这些发现并不能作为胶质瘤临床相关的预后指标。

结论

提示CREBBP和EP300的高表达水平与肿瘤体积增加呈正相关。抑制CREBBP和EP300可增强局部免疫原性,导致免疫细胞募集和细胞因子释放,从而有效根除肿瘤,最终抑制肿瘤生长。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff99/11490948/c7c861a5d3bc/10.1177_11795549241287777-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff99/11490948/8becf2b0bf7f/10.1177_11795549241287777-img2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff99/11490948/ff06285a4ebe/10.1177_11795549241287777-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff99/11490948/230126595de7/10.1177_11795549241287777-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff99/11490948/c7c861a5d3bc/10.1177_11795549241287777-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff99/11490948/8becf2b0bf7f/10.1177_11795549241287777-img2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff99/11490948/ff06285a4ebe/10.1177_11795549241287777-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff99/11490948/230126595de7/10.1177_11795549241287777-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff99/11490948/c7c861a5d3bc/10.1177_11795549241287777-fig3.jpg

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