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BRD4 高表达水平与食管鳞癌预后不良和免疫浸润相关。

High Expression Level of BRD4 Is Associated with a Poor Prognosis and Immune Infiltration in Esophageal Squamous Cell Carcinoma.

机构信息

Department of Pathology, Affiliated Hospital 2 of Nantong University and First People's Hospital of Nantong City, Shengli Road No. 666, Nantong, 226001, Jiangsu, People's Republic of China.

Medical Research Center, Affiliated Hospital 2 of Nantong University and First People's Hospital of Nantong City, Nantong, 226001, People's Republic of China.

出版信息

Dig Dis Sci. 2023 Jul;68(7):2997-3008. doi: 10.1007/s10620-023-07907-3. Epub 2023 Mar 18.

Abstract

BACKGROUND

Bromodomain-containing protein 4 (BRD4) is a reader of histone acetylation and is associated with a variety of diseases.

AIM

To investigate the expression level of BRD4 in esophageal squamous cell carcinoma (ESCC), its prognostic value and its relationship with immune infiltration.

METHODS

The study included 94 ESCC patients from The Cancer Genome Atlas (TCGA) database and 179 ESCC patients from Affiliated Hospital 2 of Nantong University. The expression levels of proteins in tissue microarray were detected by immunohistochemistry. The prognostic factors were analyzed by Kaplan-Meier curve and univariate and multivariate cox regression. The ESTIMATE website was used to calculate the stromal, immune and ESTIMATE score. CIBERSORT was used to calculate the abundance of immune infiltrates. Spearman and Phi coefficient were used for correlation analysis. The TIDE algorithm was used to predict treatment response to immune checkpoint blockade.

RESULTS

BRD4 is up-regulated in ESCC, and high BRD4 expression level is associated with poor prognosis and adverse clinicopathological features. In addition, the monocyte count, systemic inflammatory-immunologic index, platelet-lymphocyte ratio, and monocyte-lymphocyte ratio in the BRD4 high expression level group were higher than in the low expression level group. Finally, we found that BRD4 expression level correlated with immune infiltration and that it was inversely correlated with infiltration of CD8 + T cells. Higher TIDE scores in the BRD4 high expression group than in the low expression group.

CONCLUSION

BRD4 is associated with poor prognosis and immune infiltration in ESCC, and may be a potential biomarker for prognosis and immunotherapy application.

摘要

背景

溴结构域蛋白 4(BRD4)是组蛋白乙酰化的阅读器,与多种疾病有关。

目的

研究 BRD4 在食管鳞癌(ESCC)中的表达水平、其预后价值及其与免疫浸润的关系。

方法

本研究纳入了来自癌症基因组图谱(TCGA)数据库的 94 例 ESCC 患者和南通大学附属医院的 179 例 ESCC 患者。采用免疫组织化学法检测组织微阵列中蛋白质的表达水平。通过 Kaplan-Meier 曲线和单因素及多因素 Cox 回归分析预后因素。利用 ESTIMATE 网站计算基质、免疫和 ESTIMATE 评分。采用 CIBERSORT 计算免疫浸润细胞的丰度。采用 Spearman 和 Phi 系数进行相关性分析。采用 TIDE 算法预测免疫检查点阻断治疗的反应。

结果

BRD4 在 ESCC 中上调,高 BRD4 表达水平与预后不良和不良临床病理特征相关。此外,BRD4 高表达水平组的单核细胞计数、全身炎症-免疫指数、血小板-淋巴细胞比值和单核细胞-淋巴细胞比值均高于低表达水平组。最后,我们发现 BRD4 表达水平与免疫浸润相关,与 CD8+T 细胞浸润呈负相关。BRD4 高表达组的 TIDE 评分高于低表达组。

结论

BRD4 与 ESCC 的预后和免疫浸润有关,可能是预后和免疫治疗应用的潜在生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fa7/10293338/f6d6e2bcd285/10620_2023_7907_Fig1_HTML.jpg

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